bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of Antimalarial Activity at a Putative Bisquinoline Receptor In Vivo Using Fluorinated Bisquinolines
Authors: Fielding Alistair J. , Lukinović Valentina , Evans Philip G. , Alizadeh‐Shekalgourabi Said , Bisby Roger H. , Drew Michael G. B. , Male Verity , Del Casino Alessio , Dunn James F. , Randle Laura E. , Dempster Nicola M. , Nahar Lutfun , Sarker Satyajit D. , Cantú Reinhard Fabián G. , de Visser Sam P. , Dascombe Mike J. , Ismail Fyaz M. D. 
Published: March 2017

AbstractAntimalarials can interact with heme covalently, by π⋅⋅⋅π interactions or by hydrogen bonding. Consequently, the prototropy of 4‐aminoquinolines and quinoline methanols was investigated by using quantum mechanics. Calculations showed mefloquine protonated preferentially at the piperidine and was impeded at the endocyclic nitrogen because of electronic rather than steric factors. In gas‐phase calculations, 7‐substituted mono‐ and bis‐4‐aminoquinolines were preferentially protonated at the endocyclic quinoline nitrogen. By contrast, compounds with a trifluoromethyl substituent on both the 2‐ and 8‐positions, reversed the order of protonation, which now favored the exocyclic secondary amine nitrogen at the 4‐position. Loss of antimalarial efficacy by CF3 groups simultaneously occupying the 2‐ and 8‐positions was recovered if the CF3 group occupied the 7‐position. Hence, trifluoromethyl groups buttressing the quinolinyl nitrogen shifted binding of antimalarials to hematin, enabling switching from endocyclic to the exocyclic N. Both theoretical calculations (DFT calculations: B3LYP/BS1) and crystal structure of (±)‐trans‐N1,N2‐bis‐(2,8‐ditrifluoromethylquinolin‐4‐yl)cyclohexane‐1,2‐diamine were used to reveal the preferred mode(s) of interaction with hematin. The order of antimalarial activity in vivo followed the capacity for a redox change of the iron(III) state, which has important implications for the future rational design of 4‐aminoquinoline antimalarials.
Hypervalent Iodine(III)‐Mediated Cascade Cyclization of Propargylguanidines and Total Syntheses of Kealiinine B and C
Authors: Tian Guilong , Fedoseev Pavel , Van der Eycken Erik V. 
Published: March 2017

AbstractAn oxidative cascade cyclization of propargylguanidines promoted by phenyliodonium diacetate (PIDA) was developed. The protocol provides an efficient route for the synthesis of the alkaloids kealiinines B and C as well as homologues. The difference in the electronic nature of the acetylene substituent resulted in two ways of the cyclization. A plausible mechanism is proposed based on the experimental results.
Synthesis of a Dichlorosilaimine Coordinated by an N‐Heterocyclic Carbene from ArN(SiMe3)SiHCl2
Authors: Cui Haiyan , Teng Peng , Zhang Enbin , Lu Jiahao , Zhang Fan , Wu Meng 
Published: March 2017

AbstractNHC‐stabilized dichlorosilaimine ArN=Si(IiPr)Cl2 (2) (Ar = 2,6‐iPr2C6H3, IiPr = 1,3‐diisopropyl‐4,5‐dimethylimidazol‐2‐ylidene) and disilane LSiHCl‐SiCl2L (L=ArNSiMe3) (3) could be synthesized from the reaction of aminodichlorosilane ArN(SiMe3)SiHCl2 (1) with IiPr under different conditions. This represents the first route to the generation of donor‐stabilized dichlorosilaimine from substituted chlorosilane in the presence of an NHC via dehydrosilylation.
Direct Triflylation of Benzylic C—H Bonds with Pyridine as a Directing Group
Authors: Yang Jun , Hu Juanjuan , Huang Yangen , Xu Xiuhua , Qing Fengling 
Published: March 2017

AbstractThe first example of benzylic C—H triflylation was accomplished with pyridine as a directing group. The reaction of various 2‐benzylpyridines and (CF3SO2)2O in the presence of NEt3 in CH2Cl2 proceeded smoothly to afford the corresponding benzyl triflones in moderate to high yields.
Omics for Understanding the Gut‐Liver‐Microbiome Axis and Precision Medicine
Authors: Khalsa Jag , Duffy Linda C. , Riscuta Gabriela , Starke‐Reed Pamela , Hubbard Van S. 
Published: March 2017

AbstractHuman metabolic disease opens a new view to understanding the contribution of the intestinal microbiome to drug metabolism and drug‐induced toxicity in gut‐liver function. The gut microbiome, a key determinant of intestinal inflammation, also plays a direct role in chronic inflammation and liver disease. Gut bacterial communities directly metabolize certain drugs, reducing their bioavailability and influencing individual variation in drug response. In addition, some microbiome‐produced compounds may affect drug pharmacokinetics and pharmacodynamics via altered expression of metabolizing enzymes and drug transporters or genes coding for drug target proteins, drug response phenotypes, and disease states. Molecular‐based high‐throughput technologies are providing novel insight about host‐gut microbiome interactions, homeostasis, and xenobiotic effects associated with wide variation in efficacy or toxicity in humans. It is envisioned that future approaches to treating and preventing liver disease will benefit from in‐depth studies of the liver‐microbiome axis. Thus, the microbiome shares a fundamental role in human physiology with various organ systems, and its importance must be considered in the rapid evolution of precision medicine. A new emerging perspective of understanding the effect of the gut microbiome on human response to drugs would be indispensable for developing efficacious, safe, and cost‐effective precision therapies.
Intrahepatic Sampling for the Elucidation of Antiviral Clinical Pharmacology
Authors: Venuto Charles S. , Talal Andrew H. 
Published: March 2017

AbstractAlthough the importance of the liver in clinical pharmacology is widely recognized, little is known in humans concerning its function in vivo at the hepatocyte level and how pharmacological functions are altered in the setting of advanced liver disease. Several recent proof‐of‐principle studies with first‐generation DAAs have demonstrated the feasibility of serial liver sampling for pharmacological studies. These studies have begun to describe the liver‐to‐plasma concentration ratio and how this ratio is altered in the setting of advanced liver disease. These data are particularly relevant to individuals with substance‐use disorders because many have advanced liver disease as a consequence of long‐standing viral hepatitis infection or continued use of hepatotoxins such as alcohol. Future research should attempt to develop standardized and reproducible methods to assess liver drug concentration, complex drug interactions, and pharmacogenomics in humans to permit elucidation of the clinical pharmacology within the liver.
Drug–Drug Interactions and Diagnostics for Drug Users With HIV and HIV/HCV Coinfections: Introduction
Authors: Khalsa Jag H. , Talal Andrew H. , Morse Gene 
Published: March 2017

AbstractSubstance use and pharmacologic treatment of co‐occurring infections such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are associated with many adverse consequences including pharmacokinetic and pharmacodynamic drug–drug interactions (DDIs). The National Institute on Drug Abuse sponsored a 2‐day conference on DDIs at which clinicians/scientists from government, academia, and the pharmaceutical industry presented the most current research findings to formulate a comprehensive overview of DDIs. Specific topics discussed included drug metabolism; drug interactions between medications used in the treatment of HIV, HCV, and substance use disorders; intrahepatic concentrations and methods of assessment of drugs in liver disease of varying etiologies and degrees of impairment; and minimally invasive sampling techniques for the assessment of intrahepatic drug concentrations, viral replication, and changes in gene expression in response to treatment. Finally, the speakers identified research targets and priorities on DDIs. Areas of emphasis included development of diagnostic assays for drug concentration assessment in different organs, an enhanced understanding of factors responsible for alterations in drug metabolism and excretion, and establishment of clinical trials and work groups to study DDIs. Our long‐term objective is to broaden investigation in the field of DDIs in substance users.
Current Concepts in Methadone Metabolism and Transport
Authors: Kharasch Evan D. 
Published: March 2017

AbstractMethadone is a cornerstone therapy for opioid addiction and a public health strategy for HIV/AIDS and hepatitis C reduction. Methadone is also used for acute and chronic pain. As use for chronic pain has grown, so too have adverse events. Constitutive and acquired (drug interactions) inter‐ and intraindividual variability in methadone pharmacokinetics and pharmacodynamics confounds reliable clinical use. Identification of enzymes and transporters responsible for methadone disposition has been a long‐sought ideal. Initial in vitro studies identified CYP3A4 as metabolizing methadone. Subsequently, by extrapolation, CYP3A4 was long assumed to be responsible for clinical methadone disposition. However, CYP2B6 is also a major catalyst of methadone metabolism in vitro. It has now been unequivocally established that CYP2B6, not CYP3A4, is the principal determinant of methadone metabolism, clearance, elimination, and plasma concentrations in humans. Methadone disposition is susceptible to inductive and inhibitory drug interactions. CYP2B6 genetics also influences methadone metabolism and clearance, which were diminished in CYP2B6*6 carriers and increased in CYP2B6*4 carriers. CYP2B6 genetics can explain, in part, interindividual variability in methadone metabolism and clearance. Thus, both constitutive variability due to CYP2B6 genetics, and CYP2B6‐mediated drug interactions, can alter methadone disposition, clinical effect, and drug safety. Methadone is not a substrate for major influx or efflux transporters.
Determinants of Corporate Social Responsibility (CSR) Disclosure in Developed and Developing Countries: A Literature Review
Authors: Ali Waris , Frynas Jedrzej George , Mahmood Zeeshan 
Published: March 2017

AbstractBased on a survey and content analysis of 76 empirical research articles, this article reviews the factors driving Corporate Social Responsibility (CSR) disclosure in both developed and developing countries. We find that firm characteristics such as company size, industry sector, profitability, and corporate governance mechanisms predominantly appear to drive the CSR reporting agenda. Furthermore, political, social, and cultural factors influence the CSR disclosure agenda. We find crucial differences between the determinants of CSR disclosure in developed and developing countries. In developed countries, the concerns of specific stakeholders, for example, regulators, shareholders, creditors, investors, environmentalists and the media are considered very important in disclosing CSR information. In developing countries, CSR reporting is more heavily influenced by the external forces/powerful stakeholders such as international buyers, foreign investors, international media and international regulatory bodies (e.g. the World Bank). Furthermore, in contrast to developed countries, firms in developing countries perceive relatively little pressure from the public with regards to CSR disclosure. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
The impact of climate change on the distribution of two threatened Dipterocarp trees
Authors: Deb Jiban C. , Phinn Stuart , Butt Nathalie , McAlpine Clive A. 
Published: March 2017

AbstractTwo ecologically and economically important, and threatened Dipterocarp trees Sal (Shorea robusta) and Garjan (Dipterocarpus turbinatus) form mono‐specific canopies in dry deciduous, moist deciduous, evergreen, and semievergreen forests across South Asia and continental parts of Southeast Asia. They provide valuable timber and play an important role in the economy of many Asian countries. However, both Dipterocarp trees are threatened by continuing forest clearing, habitat alteration, and global climate change. While climatic regimes in the Asian tropics are changing, research on climate change‐driven shifts in the distribution of tropical Asian trees is limited. We applied a bioclimatic modeling approach to these two Dipterocarp trees Sal and Garjan. We used presence‐only records for the tree species, five bioclimatic variables, and selected two climatic scenarios (RCP4.5: an optimistic scenario and RCP8.5: a pessimistic scenario) and three global climate models (GCMs) to encompass the full range of variation in the models. We modeled climate space suitability for both species, projected to 2070, using a climate envelope modeling tool “MaxEnt” (the maximum entropy algorithm). Annual precipitation was the key bioclimatic variable in all GCMs for explaining the current and future distributions of Sal and Garjan (Sal: 49.97 ± 1.33; Garjan: 37.63 ± 1.19). Our models predict that suitable climate space for Sal will decline by 24% and 34% (the mean of the three GCMs) by 2070 under RCP4.5 and RCP8.5, respectively. In contrast, the consequences of imminent climate change appear less severe for Garjan, with a decline of 17% and 27% under RCP4.5 and RCP8.5, respectively. The findings of this study can be used to set conservation guidelines for Sal and Garjan by identifying vulnerable habitats in the region. In addition, the natural habitats of Sal and Garjan can be categorized as low to high risk under changing climates where artificial regeneration should be undertaken for forest restoration.
Linear Triplatinum Tetrahydride Complex Supported by Triphosphine Ligands, [Pt3(µ‐H)2(H)2(µ‐dpmp)2](BF4)2 {dpmp = bis(diphenylphosphinomethyl)phenylphosphine}
Authors: Tanase Tomoaki , Yamamoto Kana , Hatano Rika , Nakamae Kanako , Kure Bunsho , Ura Yasuyuki , Nakajima Takayuki 
Published: March 2017

AbstractInvited for the cover of this issue is the group of Tomoaki Tanase at Nara Women's University, Japan. The cover image shows the transformation of linear trihydride hexaplatinum complex Pt6H3 to a novel linear triplatinum tetrahydride (Pt3H4) by treatment with HBF4.
Mercury in tunas and blue marlin in the North Pacific Ocean
Authors: Drevnick Paul E. , Brooks Barbara A. 
Published: March 2017

Abstract

Models and data from the North Pacific Ocean indicate that mercury concentrations in water and biota are increasing in response to (global or hemispheric) anthropogenic mercury releases. In the present study, we provide an updated record of mercury in yellowfin tuna (Thunnus albacares) caught near Hawaii that confirms an earlier conclusion that mercury concentrations in these fish are increasing at a rate similar to that observed in waters shallower than 1000 m. We also compiled and reanalyzed data from bigeye tuna (Thunnus obesus) and blue marlin (Makaira nigricans) caught near Hawaii in the 1970s and 2000s. Increases in mercury concentrations in bigeye tuna are consistent with the trend found in yellowfin tuna, in both timing and magnitude. The data available for blue marlin do not allow for a fair comparison among years, because mercury concentrations differ between sexes for this species, and sex was identified (or reported) in only 3 of 7 studies. Also, mercury concentrations in blue marlin may be insensitive to modest changes in mercury exposure, because this species appears to have the ability to detoxify mercury. The North Pacific Ocean is a region of both relatively high rates of atmospheric mercury deposition and capture fisheries production. Other data sets that allow temporal comparisons in mercury concentrations, such as pacific cod (Gadus macrocephalus) in Alaskan waters and albacore tuna (Thunnus alalunga) off the US Pacific coast, should be explored further, to aid in understanding human health and ecological risks and to develop additional baseline knowledge for assessing changes in a region expected to respond strongly to reductions in anthropogenic mercury emissions. Environ Toxicol Chem 2017;36:1365–1374. © 2017 SETAC
New promising antifouling agent based on polymeric biocide polyhexamethylene guanidine molybdate
Authors: Protasov Alexander , Bardeau Jean-Francois , Morozovskaya Irina , Boretska Mariia , Cherniavska Tetiana , Petrus Lyudmyla , Tarasyuk Oksana , Metelytsia Larisa , Kopernyk Iryna , Kalashnikova Larisa , Dzhuzha Oleg , Rogalsky Sergiy 
Published: March 2017

Abstract

A new polymeric biocide polyhexamethylene guanidine (PHMG) molybdate has been synthesized. The obtained cationic polymer has limited water solubility of 0.015 g/100 mL and is insoluble in paint solvents. The results of acute toxicity studies indicate moderate toxicity of PHMG molybdate, which has a median lethal dose at 48 h of 0.7 mg/L for Daphnia magna and at 96 h of 17 mg/L for Danio rerio (zebrafish) freshwater model organisms. Commercial ship paint was then modified by the addition of a low concentration of polymeric biocide 5% (w/w). The painted steel panels were kept in Dnipro River water for the evaluation of the dynamics of fouling biomass. After 129-d exposure, Bryozoa dominated in biofouling of tested substrates, forming 86% (649 g/m2) of the total biomass on control panel surfaces. However, considerably lower Bryozoa fouling biomass (15 g/m2) was detected for coatings containing PHMG molybdate. Dreissenidae mollusks were found to form 88% (2182 g/m2) of the fouling biomass on the control substrates after 228 d of exposure, whereas coatings containing PHMG molybdate showed a much lower biomass value of 23.6 g/m2. The leaching rate of PHMG molybdate in water was found to be similar to rates for conventional booster biocides ranging from 5.7 μg/cm2/d at the initial stage to 2.2 μg/cm2/d at steady state. Environ Toxicol Chem 2017;36:2543–2551. © 2017 SETAC
Indirect effects of climate change on zinc cycling in sediments: The role of changing water levels
Authors: Nedrich Sara M. , Burton G. Allen 
Published: March 2017

Abstract

Increased variability in lake and river water levels associated with changing climate could impact the fate and effects of metals in redox-sensitive sediments through the alteration of microbial communities and of acid–base and redox chemistry. The objective of the present study was to determine the influence of water level fluctuation on metal speciation in porewater and predict environmental risk to high-carbonate systems. Using experimental microcosms with sediments collected from 4 metal-contaminated coastal freshwater wetlands in Michigan, USA, we conducted water level fluctuation experiments. Porewater and sediment metals (Ca, Cu, Fe, Mg, Mn, Ni, Zn) and important metal binding phases (iron-oxide speciation, acid-volatile sulfide) were quantified. In a short-term drying (seiche) experiment, there were decreases in all porewater metals after inundation of saturated sediments. During a drought experiment, re-inundation of oxidized sediments increased porewater Cu, Zn, Mg, Ca for most sites. Porewater Zn increased after inundation to levels exceeding the US Environmental Protection Agency threshold for chronic toxicity. These data show that the dissolution of metal carbonates and metal sulfates contributes to metal release after re-flooding and indicate that we might expect increased ecological risk to organisms present in drought-sensitive regions where altered hydroperiods are likely to increase metal bioavailability. Environ Toxicol Chem 2017;36:2456–2464. © 2017 SETAC
Salinity impacts on water solubility and n-octanol/water partition coefficients of selected pesticides and oil constituents
Authors: Saranjampour Parichehr , Vebrosky Emily N. , Armbrust Kevin L. 
Published: March 2017

Abstract

Salinity has been reported to influence the water solubility of organic chemicals entering marine ecosystems. However, limited data are available on salinity impacts for chemicals potentially entering seawater. Impacts on water solubility would correspondingly impact chemical sorption as well as overall bioavailability and exposure estimates used in the regulatory assessment. The pesticides atrazine, fipronil, bifenthrin, and cypermethrin, as well as the crude oil constituent dibenzothiophene together with 3 of its alkyl derivatives, all have different polarities and were selected as model compounds to demonstrate the impact of salinity on their solubility and partitioning behavior. The n-octanol/water partition coefficient (KOW) was measured in both distilled-deionized water and artificial seawater (3.2%). All compounds had diminished solubility and increased KOW values in artificial seawater compared with distilled-deionized water. A linear correlation curve estimated salinity may increase the log KOW value by 2.6%/1 log unit increase in distilled water (R2 = 0.97). Salinity appears to generally decrease the water solubility and increase the partitioning potential. Environmental fate estimates based on these parameters indicate elevated chemical sorption to sediment, overall bioavailability, and toxicity in artificial seawater. These dramatic differences suggest that salinity should be taken into account when exposure estimates are made for marine organisms. Environ Toxicol Chem 2017;36:2274–2280. © 2017 SETAC
Diffusive flux of PAHs across sediment–water and water–air interfaces at urban superfund sites
Authors: Minick D. James , Anderson Kim A. 
Published: March 2017

Abstract

Superfund sites may be a source of polycyclic aromatic hydrocarbons (PAHs) to the surrounding environment. These sites can also act as PAH sinks from present-day anthropogenic activities, especially in urban locations. Understanding PAH transport across environmental compartments helps to define the relative contributions of these sources and is therefore important for informing remedial and management decisions. In the present study, paired passive samplers were co-deployed at sediment–water and water–air interfaces within the Portland Harbor Superfund Site and the McCormick and Baxter Superfund Site. These sites, located along the Willamette River (Portland, OR, USA), have PAH contamination from both legacy and modern sources. Diffusive flux calculations indicate that the Willamette River acts predominantly as a sink for low molecular weight PAHs from both the sediment and the air. The sediment was also predominantly a source of 4- and 5-ring PAHs to the river, and the river was a source of these same PAHs to the air, indicating that legacy pollution may be contributing to PAH exposure for residents of the Portland urban center. At the remediated McCormick and Baxter Superfund Site, flux measurements highlight locations within the sand and rock sediment cap where contaminant breakthrough is occurring. Environ Toxicol Chem 2017;36:2281–2289. © 2017 SETAC