-
Bioorganic & Medicinal Chemistry Dec 2017
Topics: Chemistry, Pharmaceutical; Drug Industry; Organic Chemicals; Pharmaceutical Preparations
PubMed: 29153554
DOI: 10.1016/j.bmc.2017.11.013 -
Environmental Health Perspectives Dec 2021Large numbers of chemicals require evaluation to determine if their production and use pose potential risks to ecological and human health. For most chemicals, the...
BACKGROUND
Large numbers of chemicals require evaluation to determine if their production and use pose potential risks to ecological and human health. For most chemicals, the inadequacy and uncertainty of chemical-specific data severely limit the application of exposure- and risk-based methods for screening-level assessments, priority setting, and effective management.
OBJECTIVE
We developed and evaluated a holistic, mechanistic modeling framework for ecological and human health assessments to support the safe and sustainable production, use, and disposal of organic chemicals.
METHODS
We consolidated various models for simulating the PROduction-To-EXposure (PROTEX) continuum with empirical data sets and models for predicting chemical property and use function information to enable high-throughput (HT) exposure and risk estimation. The new PROTEX-HT framework calculates exposure and risk by integrating mechanistic computational modules describing chemical behavior and fate in the socioeconomic system (i.e., life cycle emissions), natural and indoor environments, various ecological receptors, and humans. PROTEX-HT requires only molecular structure and chemical tonnage (i.e., annual production or consumption volume) as input information. We evaluated the PROTEX-HT framework using 95 organic chemicals commercialized in the United States and demonstrated its application in various exposure and risk assessment contexts.
RESULTS
Seventy-nine percent and 97% of the PROTEX-HT human exposure predictions were within one and two orders of magnitude, respectively, of independent human exposure estimates inferred from biomonitoring data. PROTEX-HT supported screening and ranking chemicals based on various exposure and risk metrics, setting chemical-specific maximum allowable tonnage based on user-defined toxicological thresholds, and identifying the most relevant emission sources, environmental media, and exposure routes of concern in the PROTEX continuum. The case study shows that high chemical tonnage did not necessarily result in high exposure or health risks.
CONCLUSION
Requiring only two chemical-specific pieces of information, PROTEX-HT enables efficient screening-level evaluations of existing and premanufacture chemicals in various exposure- and risk-based contexts. https://doi.org/10.1289/EHP9372.
Topics: Environmental Exposure; Humans; Organic Chemicals; Risk Assessment; Uncertainty; United States
PubMed: 34882502
DOI: 10.1289/EHP9372 -
Annual Review of Physical Chemistry Apr 2015Mechanisms of bimolecular chemical reactions in solution are amenable to study on picosecond timescales, both by transient absorption spectroscopy and by computer... (Review)
Review
Mechanisms of bimolecular chemical reactions in solution are amenable to study on picosecond timescales, both by transient absorption spectroscopy and by computer simulation. The dynamics of exothermic reactions of CN radicals and of Cl and F atoms with organic solutes in commonly used solvents are contrasted with the corresponding dynamics in the gas phase. Many characteristics of the gas-phase reaction dynamics persist in solution, such as efficient energy release to specific vibrational modes of the products. However, additional complexities associated with the presence of the solvent are open to investigation. These features of liquid-phase reactions include the role of solvent-solute complexes, solvent caging, coupling of the product motions to the solvent bath, thermalization of internally excited reaction products, incipient hydrogen bond formation, and involvement of charge-separated states that arise from proton transfer.
Topics: Chlorine; Fluorine; Free Radicals; Models, Molecular; Nitriles; Organic Chemicals; Photochemical Processes; Solutions; Solvents
PubMed: 25830373
DOI: 10.1146/annurev-physchem-040214-121654 -
Current Medicinal Chemistry 2019Self-assembled fluorescent nanomaterials based on small-molecule organic dyes are gaining increasing popularity in imaging and sensing applications over the past decade.... (Review)
Review
Self-assembled fluorescent nanomaterials based on small-molecule organic dyes are gaining increasing popularity in imaging and sensing applications over the past decade. This is primarily due to their ability to combine spectral properties tunability and biocompatibility of small molecule organic fluorophores with brightness, chemical and colloidal stability of inorganic materials. Such a unique combination of features comes with rich versatility of dye-based nanomaterials: from aggregates of small molecules to sophisticated core-shell nanoarchitectures involving hyperbranched polymers. Along with the ongoing discovery of new materials and better ways of their synthesis, it is very important to continue systematic studies of fundamental factors that regulate the key properties of fluorescent nanomaterials: their size, polydispersity, colloidal stability, chemical stability, absorption and emission maxima, biocompatibility, and interactions with biological interfaces. In this review, we focus on the systematic description of various types of organic fluorescent nanomaterials, approaches to their synthesis, and ways to optimize and control their characteristics. The discussion is built on examples from reports on recent advances in the design and applications of such materials. Conclusions made from this analysis allow a perspective on future development of fluorescent nanomaterials design for biomedical and related applications.
Topics: Fluorescent Dyes; Molecular Conformation; Nanostructures; Optical Imaging; Organic Chemicals; Small Molecule Libraries
PubMed: 29484973
DOI: 10.2174/0929867325666180226111716 -
Molecules (Basel, Switzerland) Sep 2015In the rapidly developing areas of nanotechnology, nano-scale materials as heterogeneous catalysts in the synthesis of organic molecules have gotten more and more... (Review)
Review
In the rapidly developing areas of nanotechnology, nano-scale materials as heterogeneous catalysts in the synthesis of organic molecules have gotten more and more attention. In this review, we will summarize the synthesis of several new types of noble metal nanostructures (FePt@Cu nanowires, Pt@Fe₂O₃ nanowires and bimetallic Pt@Ir nanocomplexes; Pt-Au heterostructures, Au-Pt bimetallic nanocomplexes and Pt/Pd bimetallic nanodendrites; Au nanowires, CuO@Ag nanowires and a series of Pd nanocatalysts) and their new catalytic applications in our group, to establish heterogeneous catalytic system in "green" environments. Further study shows that these materials have a higher catalytic activity and selectivity than previously reported nanocrystal catalysts in organic reactions, or show a superior electro-catalytic activity for the oxidation of methanol. The whole process might have a great impact to resolve the energy crisis and the environmental crisis that were caused by traditional chemical engineering. Furthermore, we hope that this article will provide a reference point for the noble metal nanomaterials' development that leads to new opportunities in nanocatalysis.
Topics: Catalysis; Copper; Electrochemistry; Green Chemistry Technology; Nanowires; Organic Chemicals; Platinum; Silver; Surface Properties
PubMed: 26393550
DOI: 10.3390/molecules200917070 -
Environmental Research Oct 2015Epidemiological evidence supports associations between prenatal exposure to environmental organic chemicals and childhood health impairments. Unlike the common choice of... (Review)
Review
Epidemiological evidence supports associations between prenatal exposure to environmental organic chemicals and childhood health impairments. Unlike the common choice of biological matrices such as urine and blood that can be limited by short half-lives for some chemicals, teeth provide a stable repository for chemicals with half-life in the order of decades. Given the potential of the tooth bio-matrix to study long-term exposures to environmental organic chemicals in human biomonitoring programs, it is important to be aware of possible pitfalls and potential opportunities to improve on the current analytical method for tooth organics analysis. We critically review previous results of studies of this topic. The major drawbacks and challenges in currently practiced concepts and analytical methods in utilizing tooth bio-matrix are (i) no consideration of external (from outer surface) or internal contamination (from micro-odontoblast processes), (ii) the misleading assumption that whole ground teeth represent prenatal exposures (latest formed dentine is lipid rich and therefore would absorb and accumulate more organic chemicals), (iii) reverse causality in exposure assessment due to whole ground teeth, and (iv) teeth are a precious bio-matrix and grinding them raises ethical concerns about appropriate use of a very limited resource in exposure biology and epidemiology studies. These can be overcome by addressing the important limitations and possible improvements with the analytical approach associated at each of the following steps: (i) tooth sample preparation to retain exposure timing, (ii) organics extraction and pre-concentration to detect ultra-trace levels of analytes, (iii) chromatography separation, (iv) mass spectrometric detection to detect multi-class organics simultaneously, and (v) method validation, especially to exclude chance findings. To highlight the proposed improvements we present findings from a pilot study that utilizes tooth matrix biomarkers to obtain trimester-specific exposure information for a range of organic chemicals.
Topics: Biomarkers; Environmental Monitoring; Environmental Pollutants; Female; Humans; Organic Chemicals; Pregnancy; Prenatal Exposure Delayed Effects; Tooth, Deciduous
PubMed: 26219084
DOI: 10.1016/j.envres.2015.06.032 -
Molecules (Basel, Switzerland) Oct 2015Starch has been an inexhaustible subject of research for many decades. It is an inexpensive, readily-available material with extensive application in the food and... (Review)
Review
Starch has been an inexhaustible subject of research for many decades. It is an inexpensive, readily-available material with extensive application in the food and processing industry. Researchers are continually trying to improve its properties by different modification procedures and expand its application. What is mostly applied in this view are their chemical modifications, among which organic acids have recently drawn the greatest attention, particularly with respect to the application of starch in the food industry. Namely, organic acids naturally occur in many edible plants and many of them are generally recognized as safe (GRAS), which make them ideal modification agents for starch intended for the food industry. The aim of this review is to give a short literature overview of the progress made in the research of starch esterification, etherification, cross-linking, and dual modification with organic acids and their derivatives.
Topics: Acetylation; Cross-Linking Reagents; Dicarboxylic Acids; Esterification; Ethers; Fatty Acids; Food Industry; Organic Chemicals; Spectroscopy, Fourier Transform Infrared; Starch; Succinic Anhydrides
PubMed: 26516831
DOI: 10.3390/molecules201019554 -
The Journal of Organic Chemistry Dec 2009From a scientific perspective, efforts to understand biology including what constitutes health and disease has become a chemical problem. However, chemists and... (Review)
Review
From a scientific perspective, efforts to understand biology including what constitutes health and disease has become a chemical problem. However, chemists and biologists "see" the problems of understanding biology from different perspectives, and this has retarded progress in solving the problems especially as they relate to health and disease. This suggests that close collaboration between chemists and biologists is not only necessary but essential for progress in both the biology and chemistry that will provide solutions to the global questions of biology. This perspective has directed my scientific efforts for the past 45 years, and in this overview I provide my perspective of how the applications of synthetic chemistry, structural design, and numerous other chemical principles have intersected in my collaborations with biologists to provide new tools, new science, and new insights that were only made possible and fruitful by these collaborations.
Topics: Biology; Chemistry, Organic; Chemistry, Pharmaceutical; Drug Design; International Cooperation; Organic Chemicals
PubMed: 20000552
DOI: 10.1021/jo901767e -
The Journal of Toxicological Sciences 2016A wide variety of drugs and chemicals have been shown to produce induction and inhibition of heme-metabolizing enzymes, and of drug-metabolizing enzymes, including... (Review)
Review
A wide variety of drugs and chemicals have been shown to produce induction and inhibition of heme-metabolizing enzymes, and of drug-metabolizing enzymes, including cytochrome P450s (P450s, CYPs), which consist of many molecular species with lower substrate specificity. Such chemically induced enzyme alterations are coordinately or reciprocally regulated through the same and/or different signal transductions. From the toxicological point of view, these enzymatic changes sometimes exacerbate inherited diseases, such as precipitation of porphyrogenic attacks, although the induction of these enzymes is dependent on the animal species in response to the differences in the stimuli of the liver, where they are also metabolized by P450s. Since P450s are hemoproteins, their induction and/or inhibition by chemical compounds could be coordinately accompanied by heme synthesis and/or inhibition. This review will take a retrospective view of research works carried out in our department and current findings on chemical-induced changes in hepatic heme metabolism in many places, together with current knowledge. Specifically, current beneficial aspects of induction of heme oxygenase-1, a rate-limiting heme degradation enzyme, and its relation to reciprocal and coordinated changes in P450s, with special reference to CYP2A5, in the liver are discussed. Mechanistic studies are also summarized in relation to current understanding on these aspects. Emphasis is also paid to an example of a single chemical compound that could cause various changes by mediating multiple signal transduction systems. Current toxicological studies have been developing by utilizing a sophisticated "omics" technology and survey integrated changes in the tissues produced by the administration of a chemical, even in time- and dose-dependent manners. Toxicological studies are generally carried out step by step to determine and elucidate mechanisms produced by drugs and chemicals. Such approaches are correct; however, current "omics" technology can clarify overall changes occurring in the cells and tissues after treating animals with drugs and chemicals, integrate them and discuss the results. In the present review, we will discuss chemical-induced similar changes of heme synthesis and degradation, and of P450s and finally convergence to similar or different directions.
Topics: Aminolevulinic Acid; Animals; Cytochrome P-450 Enzyme System; Enzyme Induction; Heme; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Humans; Liver; Organic Chemicals; Rodentia; Toxicology; Transcription Factors
PubMed: 28320986
DOI: 10.2131/jts.41.SP89 -
Environmental Toxicology and Chemistry Apr 2022With improved analytical techniques, environmental monitoring studies are increasingly able to report the occurrence of tens or hundreds of chemicals per site, making it...
With improved analytical techniques, environmental monitoring studies are increasingly able to report the occurrence of tens or hundreds of chemicals per site, making it difficult to identify the most relevant chemicals from a biological standpoint. For the present study, organic chemical occurrence was examined, individually and as mixtures, in the context of potential biological effects. Sediment was collected at 71 Great Lakes (USA/Canada) tributary sites and analyzed for 87 chemicals. Multiple risk-based lines of evidence were used to prioritize chemicals and locations, including comparing sediment concentrations and estimated porewater concentrations with established whole-organism benchmarks (i.e., sediment and water quality criteria and screening values) and with high-throughput toxicity screening data from the US Environmental Protection Agency's ToxCast database, estimating additive effects of chemical mixtures on common ToxCast endpoints, and estimating toxic equivalencies for mixtures of alkylphenols and polycyclic aromatic hydrocarbons (PAHs). This multiple-lines-of-evidence approach enabled the screening of more chemicals, mitigated the uncertainties of individual approaches, and strengthened common conclusions. Collectively, at least one benchmark/screening value was exceeded for 54 of the 87 chemicals, with exceedances observed at all 71 of the monitoring sites. Chemicals with the greatest potential for biological effects, both individually and as mixture components, were bisphenol A, 4-nonylphenol, indole, carbazole, and several PAHs. Potential adverse outcomes based on ToxCast gene targets and putative adverse outcome pathways relevant to individual chemicals and chemical mixtures included tumors, skewed sex ratios, reproductive dysfunction, hepatic steatosis, and early mortality, among others. The results provide a screening-level prioritization of chemicals with the greatest potential for adverse biological effects and an indication of sites where they are most likely to occur. Environ Toxicol Chem 2022;41:1016-1041. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Topics: Environmental Monitoring; Lakes; Polycyclic Aromatic Hydrocarbons; Water Pollutants, Chemical; Water Quality
PubMed: 35170813
DOI: 10.1002/etc.5286