Isomer-Specific Accumulation of Perfluorooctanesulfonate from (<i>N</i>‑Ethyl perfluorooctanesulfonamido)ethanol-based Phosphate Diester in Japanese Medaka (Oryzias latipes)

While (<i>N</i>-ethyl perfluorooctanesulfonamido)­ethanol (FOSE) -based phosphate diester (diSPAP) has been proposed as a candidate precursor of perfluorooctanesulfonate (PFOS), its potential biotransformation to PFOS has not been verified. Metabolism of diSPAP was investigated in Japanese medaka (Oryzias latipes) after exposure in water for 10 days, followed by 10 days of depuration. Branched isomers of diSPAP (B-diSPAP) were preferentially enriched in medaka exposed to diSPAP, with the proportion of branched isomers (BF) ranging from 0.56 to 0.80, which was significantly greater than that in the water to which the medaka were exposed (0.36) (<i>p</i> < 0.001). This enrichment was due primarily to preferential uptake of B-diSPAP. PFOS together with perfluorooctanesulfonamide (PFOSA), <i>N</i>-ethyl perfluorooctanesulfonamide (NEtFOSA), 2-(perfluorooctanesulfonamido)­acetic acid (FOSAA), NEtFOSAA, FOSE, and NEtFOSE were detected in medaka exposed to diSPAP, which indicated the potential for biotransformation of diSPAP to PFOS via multiple intermediates. Due to preferential metabolism of branched isomers, FOSAA and PFOSA exhibited greater BF values (>0.5) than those of NEtFOSA, NEtFOSAA, and NEtFOSE (<0.2). Such preferential metabolism of branched isomers along the primary pathway of metabolism and preferential accumulation of B-diSPAP led to enrichment of branched PFOS (B-PFOS) in medaka. Enrichment of B-PFOS was greater for 3-, 4-, and 5-perfluoromethyl PFOS (P₃MPFOS, P₄MPFOS, and P₅MPFOS), for which values of BF were 0.58 ± 0.07, 0.62 ± 0.06, and 0.61 ± 0.05 (day 6), respectively; these values are 5.8-, 7.8-, and 6.4-fold greater than those of technical PFOS. This work provides evidence on the isomer-specific accumulation of PFOS from diSPAP and will be helpful to track indirect sources of PFOS in the future

Facile Synthesis of Clickable, Water-Soluble, and Degradable Polyphosphoesters

“Click” chemistry is a library of efficient and reliable reactions, which have been used to functionalize various classes of bio- and synthetic macromolecular systems for the incorporation of designed properties and functions. In this report, azide–alkyne Huisgen cycloaddition and thiol-yne reactions, two classical “click” chemistries, were employed to functionalize biodegradable, clickable polyphosphoester homopolymers, and their water-soluble copolymers. A stable alkyne-functionalized phospholane monomer was synthesized, its organocatalyzed polymerization kinetics were evaluated, and the resulting (co)­polymers were utilized to develop this facile method that provides the synthesis of clickable, water-soluble, and degradable polyphosphoesters, which can be adapted for various applications

<i>p</i>,<i>p</i>′‑DDE Induces Gonadal Intersex in Japanese Medaka (<i>Oryzias latipes</i>) at Environmentally Relevant Concentrations: Comparison with <i>o</i>,<i>p</i>′‑DDT

Previous studies have reported high body burdens of dichlorodiphenyltrichloroethane (DDT) and its metabolites in wild fishes worldwide. This study evaluated the adverse effects of 1,1-dichloro-2,2-bis (<i>p</i>-chlorophenyl)-ethylene (<i>p</i>,<i>p</i>′-DDE) and <i>o</i>,<i>p</i>′<i>-</i>DDT on gonadal development and reproduction by exposing transgenic Japanese medaka (<i>Oryzias latipes</i>) from hatch for 100 days. While both <i>p</i>,<i>p</i>′-DDE and <i>o</i>,<i>p</i>′-DDT induced intersex in male medaka, the lowest observable effective concentration (LOEC) of <i>o</i>,<i>p</i>′-DDT was 57.7 ng/g ww, about 5-fold lower than that (272 ng/g ww) of <i>p</i>,<i>p</i>′-DDE. Since LOECs of both chemicals were comparable to the body concentrations in wild fish, DDT contamination would likely contribute to the occurrence of intersex observed in wild fish. Exposure to <i>o</i>,<i>p</i>′-DDT resulted in much higher expression of vitellogenin in liver of males than <i>p</i>,<i>p</i>′-DDE, accordant with the higher potency of <i>o</i>,<i>p</i>′-DDT than <i>p</i>,<i>p</i>′-DDE to induce intersex. This phenomenon could be partly explained by the significantly elevated levels of 17β-estradiol in plasma of males exposed to <i>o</i>,<i>p</i>′-DDT, in addition to its estrogenic activity via the estrogen receptor. Significantly lower fertilization (<i>p</i> = 0.006) and hatchability (<i>p</i> = 0.019) were observed in the 13 intersex males. This study for the first time demonstrated the induction of intersex and reproductive effects of <i>p</i>,<i>p</i>′-DDE and <i>o</i>,<i>p</i>′-DDT at environmentally relevant concentrations

Adverse Effects of Triclosan and Binary Mixtures with 17β-Estradiol on Testicular Development and Reproduction in Japanese Medaka (<i>Oryzias latipes</i>) at Environmentally Relevant Concentrations

Considering triclosan (TCS) is ubiquitous in surface water and wild fish at relatively high concentrations, its adverse effects on gonadal development and reproduction were evaluated. After exposure for 100 days after hatching, the lowest observable effective concentration (LOEC) of TCS to significantly induce gonadal intersex in male Japanese medaka (<i>Oryzias latipes</i>) was 117.9 ng/L. Courtship frequency and hatching rates in male medaka were significantly inhibited, and the LOECs of TCS to impact courtship frequency and hatching rates were 117.9 and 17.2 ng/L, respectively. Male medaka were also exposed to binary mixtures of 2.2 ng/L 17β-estradiol (βE2) with 2.3 ng/L TCS and 2.4 ng/L βE2 with 117.9 ng/L TCS, and a more severe intersex induction and depressed mating behavior compared to those seen after exposure to only βE2 or TCS were observed. The adverse effects of TCS and binary mixtures with βE2 on testicular development and reproduction in fish at environmentally relevant concentrations are demonstrated here for the first time

Synthesis and Direct Visualization of Dumbbell-Shaped Molecular Brushes

Dumbbell-shaped triblock molecular brushes were synthesized by ring-opening metathesis polymerization (ROMP) of poly­(lactide) macromonomers with terminal norbornene groups (NB-PLA) in a sequential addition manner. By changing the macromonomer size and the feed ratio of Grubbs’ catalyst to macromonomer, the dimensions of the “ball” and “bar” of the dumbbell-shaped molecular brushes were controlled. The growth and production of well-defined structures were verified by gel permeation chromatography (GPC), and the final dumbbell-shaped architectures were visualized by atomic force microscopy (AFM). This synthetic methodology represents a rapid and convenient route to unique macromolecular topologies

Robust Magnetic/Polymer Hybrid Nanoparticles Designed for Crude Oil Entrapment and Recovery in Aqueous Environments

Well-defined, magnetic shell cross-linked knedel-like nanoparticles (MSCKs) with hydrodynamic diameters <i>ca.</i> 70 nm were constructed through the co-assembly of amphiphilic block copolymers of PAA₂₀-<i>b</i>-PS₂₈₀ and oleic acid-stabilized magnetic iron oxide nanoparticles using tetrahydrofuran, <i>N</i>,<i>N</i>-dimethylformamide, and water, ultimately transitioning to a fully aqueous system. These hybrid nanomaterials were designed for application as sequestering agents for hydrocarbons present in crude oil, based upon their combination of amphiphilic organic domains, for aqueous solution dispersibility and capture of hydrophobic guest molecules, with inorganic core particles for magnetic responsivity. The employment of these MSCKs in a contaminated aqueous environment resulted in the successful removal of the hydrophobic contaminants at a ratio of 10 mg of oil per 1 mg of MSCK. Once loaded, the crude oil-sorbed nanoparticles were easily isolated <i>via</i> the introduction of an external magnetic field. The recovery and reusability of these MSCKs were also investigated. These results suggest that deployment of hybrid nanocomposites, such as these, could aid in environmental remediation efforts, including at oil spill sites, in particular, following the bulk recovery phase

Equol Induces Gonadal Intersex in Japanese Medaka (<i>Oryzias latipes</i>) at Environmentally Relevant Concentrations: Comparison with 17β-Estradiol

Equol is present in the aquatic environment via livestock waste and runoff discharge; however, it remains unclear whether it can induce gonadal intersex in fish at environmentally relevant concentrations. This study evaluated adverse effects of equol on gonadal development by exposing transgenic Japanese medaka (<i>Oryzias latipes</i>) from hatching for 100 days. Equol induced intersex incidence in male medaka in a dose-dependent manner, and the benchmark dose corresponding to 10% intersex incidence (BMD₁₀) was 11.5 ng/L (95% confidence interval (CI): 5.8 ng/L, 19.8 ng/L), which was comparable to the required dose of 17β-estradiol (E2β) (9.0 ng/L, 95% CI: 6.6 ng/L, 11.0 ng/L). Equol exposure resulted in reduced plasma 11-ketotestosterone (11-KT) concentrations in male medaka at 1.3 ng/L, while reduced plasma 11-KT concentrations were observed at a relatively high concentration (6.4 ng/L) of E2β. Such antiandrogenic property could partly explain the comparable potency of equol with that of E2β to induce intersex at relatively low concentrations, although the binding affinity of equol to medaka estrogen receptor α (EC₅₀ 939.4 nM) was 230-fold lower than that (4.07 nM) of E2β. This study for the first time demonstrated that equol could induce intersex in medaka fish at environmentally relevant concentrations

Polyphosphoramidates That Undergo Acid-Triggered Backbone Degradation

The direct and facile synthesis of polyphosphoramidates (PPAs) with acid-labile phosphoramidate backbone linkages are reported, together with demonstration of their hydrolytic degradability, evaluated under acidic conditions. The introduction of acid-labile linkages along the polymer backbone led to rapid degradation of the polymer backbone dependent upon the environmental stimuli. An oxazaphospholidine monomer bearing a phosphoramidate linkage was designed and synthesized to afford the PPAs via organobase-catalyzed ring-opening polymerization in a controlled manner. The hydrolytic degradation of the PPAs was studied, revealing breakdown of the polymer backbone through cleavage of the phosphoramidate linkages under acidic conditions

Poly(d‑glucose carbonate) Block Copolymers: A Platform for Natural Product-Based Nanomaterials with Solvothermatic Characteristics

A natural product-based polymer platform, having the characteristics of being derived from renewable materials and capable of breaking down, ultimately, into natural byproducts, has been prepared through the ring-opening polymerization (ROP) of a glucose-based bicyclic carbonate monomer. ROP was carried out via chain extension of a polyphosphoester (PPE) macroinitiator in the presence of 1,5,7-triazabicyclo[4.4.0]­dec-5-ene (TBD) organocatalyst to afford the PPE-<i>b</i>-poly­(d-glucose carbonate) (PDGC) block copolymer. This new copolymer represents a functional architecture that can be rapidly transformed through thiol-yne reactions along the PPE segment into a diverse variety of amphiphilic polymers, which interestingly display stimuli-sensitive phase behavior in the form of a lower critical solution temperature (LCST). Below the LCST, they undergo self-assembly to form spherical core–shell nanostructures that display a poorly defined core–shell morphology. It is expected that hydrophobic patches are exposed within the micellar corona, reminiscent of the surface complexity of proteins, making these materials of interest for triggered and reversible assembly disassembly processes

Rapid and Versatile Construction of Diverse and Functional Nanostructures Derived from a Polyphosphoester-Based Biomimetic Block Copolymer System

A rapid and efficient approach for the preparation and modification of a versatile class of functional polymer nanoparticles has been developed, for which the entire engineering process from small molecules to polymers to nanoparticles bypasses typical slow and inefficient procedures and rather employs a series of steps that capture fully the “click” chemistry concepts that have greatly facilitated the preparation of complex polymer materials over the past decade. The construction of various nanoparticles with functional complexity from a versatile platform is a challenging aim to provide materials for fundamental studies and also optimization toward a diverse range of applications. In this paper, we demonstrate the rapid and facile preparation of a family of nanoparticles with different surface charges and functionalities based on a biodegradable polyphosphoester block copolymer system. From a retrosynthetic point of view, the nonionic, anionic, cationic, and zwitterionic micelles with hydrodynamic diameters between 13 and 21 nm and great size uniformity were quickly formed by suspending, independently, four amphiphilic diblock polyphosphoesters into water, which were functionalized from the same parental hydrophobic-functional AB diblock polyphosphoester by click-type thiol–yne reactions. The well-defined (PDI < 1.2) hydrophobic-functional AB diblock polyphosphoester was synthesized by an ultrafast (<5 min) organocatalyzed ring-opening polymerization in a two-step, one-pot manner with the quantitative conversions of two kinds of cyclic phospholane monomers. The whole programmable process starting from small molecules to nanoparticles could be completed within 6 h, as the most rapid approach for the anionic and nonionic nanoparticles, although the cationic and zwitterionic nanoparticles required ca. 2 days due to purification by dialysis. The micelles showed high biocompatibility, with even the cationic micelles exhibiting a 6-fold lower cytotoxicity toward RAW 264.7 mouse macrophage cells, as compared to the commercial transfection agent Lipofectamine