An Efficient, Amine-Specific, and Cost-Effective Method for TMT 6/11-plex Labeling Improves the Proteome Coverage, Quantitative Accuracy and Precision.

Tandem mass tags (TMT) are widely used in proteomics to simultaneously quantify multiple samples in a single experiment. The tags can be easily added to the primary amines of peptides/proteins through chemical reactions. In addition to amines, TMT reagents also partially react with the hydroxyl groups of serine, threonine, and tyrosine residues under alkaline conditions, which significantly compromises the analytical sensitivity and precision. Under alkaline conditions, reducing the TMT molar excess can partially mitigate overlabeling of histidine-free peptides, but has a limited effect on peptides containing histidine and hydroxyl groups. Here, we present a method under acidic conditions to suppress overlabeling while efficiently labeling amines, using only one-fifth of the TMT amount recommended by the manufacturer. In a deep-scale analysis of a yeast/human two-proteome sample, we systematically evaluated our method against the manufacturer's method and a previously reported TMT-reduced method. Our method reduced overlabeled peptides by 9-fold and 6-fold, respectively, resulting in the substantial enhancement in peptide/protein identification rates. More importantly, the quantitative accuracy and precision were improved as overlabeling was reduced, endowing our method with greater statistical power to detect 42% and 12% more statistically significant yeast proteins compared to the standard and TMT-reduced methods, respectively. Mass spectrometric data have been deposited in the ProteomeXchange Consortium via the iProX partner repository with the data set identifier PXD047052.

Occurrence, multiphase partition and risk assessment of organic amine pesticides in drinking water source of Xiang River, China.

The extensive use of organic amine pesticides (OAPs) in agricultural practices has resulted in the contamination of water environments, posing threats to ecosystems and human health. This study focused on the Xiang River (XR), a representative drinking water source, as the research area to investigate the occurrence characteristics of 34 OAPs. Diphenylamine emerged as the most prevalent OAP in surface water due to industrial and agricultural activities, while cycloate dominated in sediments due to cumulative effects. Generally, the concentration of OAPs in a mixed tap water sample was lower than those in surface water samples, indicating OAPs can be removed by water plants to a certain extent. The water-sediment distribution coefficients (kd) of ΣOAPs were much less than 1 L/g, the majority of OAPs maintained relatively high concentrations in water samples instead of accumulating in sediments. Furthermore, risk assessment revealed that carbofuran showed a moderate risk to the aquatic environment, with a risk quotient of 0.23, while other OAPs presented minor risks. This study provided crucial insights for regional pesticide management and control in the XR basin, emphasizing the importance of implementing strategies to minimize the release of OAPs into the environment and protect human health.

Assessment of Amino Acid Electrostatic Parametrizations of the Polarizable Gaussian Multipole Model.

Accurate parametrization of amino acids is pivotal for the development of reliable force fields for molecular modeling of biomolecules such as proteins. This study aims to assess amino acid electrostatic parametrizations with the polarizable Gaussian Multipole (pGM) model by evaluating the performance of the pGM-perm (with atomic permanent dipoles) and pGM-ind (without atomic permanent dipoles) variants compared to the traditional RESP model. The 100-conf-combterm fitting strategy on tetrapeptides was adopted, in which (1) all peptide bond atoms (-CO-NH-) share identical set of parameters and (2) the total charges of the two terminal N-acetyl (ACE) and N-methylamide (NME) groups were set to neutral. The accuracy and transferability of electrostatic parameters across peptides with varying lengths and real-world examples were examined. The results demonstrate the enhanced performance of the pGM-perm model in accurately representing the electrostatic properties of amino acids. This insight underscores the potential of the pGM-perm model and the 100-conf-combterm strategy for the future development of the pGM force field.

Wireless Sensor for Meat Freshness Assessment Based on Radio Frequency Communication.

Wireless communication technologies, particularly radio frequency (RF), have been widely explored for wearable electronics with secure and user-friendly information transmission. By exploiting the operational principle of chemically actuated resonant devices (CARDs) and the electrical response observed in chemiresistive materials, we propose a simple and hands-on alternative to design and manufacture RF tags that function as CARDs for wireless sensing of meat freshness. Specifically, the RF antennas were meticulously designed and fabricated by lithography onto a flexible substrate with conductive tape, and the RF signal was characterized in terms of amplitude and peak resonant frequency. Subsequently, a single-walled carbon nanotube (SWCNT)/MoS2/In2O3 chemiresistive composite was incorporated into the RF tag to convey it as CARDs. The RF signal was then utilized to establish a correlation between the sensor's electrical response and the RF attenuation signal (reflection coefficient) in the presence of volatile amines and seafood (shrimp) samples. The freshness of the seafood samples was systematically assessed throughout the storage time by utilizing the CARDs, thereby underscoring their effective potential for monitoring food quality. Specifically, the developed wireless tags provide cumulative amine exposure data within the food package, demonstrating a gradual decrease in radio frequency signals. This study illustrates the versatility of RF tags integrated with chemiresistors as a promising pathway toward scalable, affordable, and portable wireless chemical sensors.

Marketable 1,3-dimethylamylamine and caffeine-based thermogenic supplements: Regulatory genotoxicity assessment through in vitro and in silico approaches.

The consumption of dietary supplements to enhance physical performance has increased significantly in the last century, especially thermogenic pre-workout supplements. Nevertheless, this industry has faced criticism for inadequate safety measures surveillance in regulatory issues regarding their products. The aims of our study were to investigate two pre-workout supplements with respect to (1) mutagenicity utilizing Salmonella/microsome assay; (2) genotoxicity employing cytokinesis-block micronucleus (CBMN) assay protocols; and (3) hepatocytoxicity using WST cell proliferation, activities of lactate dehydrogenase (LDH) and alkaline phosphatase using human liver carcinoma (HepG2) and mouse fibroblast (F C3H) cells. Oxidative stress was determined through glutathione (GSH) measurement and in silico for predictions of pharmacokinetics and toxicity for the most abundant isolated substances present in these supplements. Both supplements induced mutagenicity in all examined bacterial strains, especially in the presence of exogenous metabolism. Further, tested supplements significantly elevated the formation of micronuclei (MN) as well as other cellular phenomena. Concentration- and time-dependent curves were observed for hepatotoxicity in both studied cell lines. In addition, both supplements decreased levels of intracellular and extracellular GSH. In silico predictions showed that the isolated individual compounds failed to induce the observed outcomes. Our findings provide contributions to the molecular mechanisms underlying two pre-workout supplement-induced toxicity and the need for surveillance.

Green and economic flame retardant prepared by the one-step method for polylactic acid.

Resolving the flammability of poly(L-lactic acid) (PLA) while ensuring its environmental friendliness and preserving key flame retardancy and mechanical properties represents a critical challenge. We have successfully developed a highly efficient and environmentally friendly flame retardant called Hexamethylenediamine tetramethylene phosphonic acid amine (HDME). The flame retardancy of PLA/HDME composites was significantly improved, as indicated by the LOI value of 29.1 % and UL-94 V-0 rating for PLA/3.5 HDME with only 3.5 % HDME addition. The results show a 23.4 % reduction in the total heat release (THR), a 40.0 % increase in the time to ignition (TTI), and a 21.2 % increase in the flame propagation index (FPI) compared to original PLA. Flame retardant mechanism of HDME involves the gas phase, condensed phase, and interrupted heat exchange effects. The HDME also preserved the original mechanical properties of PLA, with the elongation at break and tensile strength retention of PLA/3.5 HDME reaching 93.05 % and 89.65 %. This work provides a simple and efficient method for flame retardant modification of PLA, which can expand its application scope.

Synthesis and application of quaternary amine-functionalized core-shell-shell magnetic polymers for determination of metabolites of benzene, toluene and xylene in human urine samples and study of exposure assessment.

As production processes have evolved, airborne concentrations of benzene, toluene and xylene in many workplaces are already well below the occupational exposure limits. However, studies have shown that low levels of exposure to benzene, toluene and xylene can still cause health effects in people exposed occupationally. However, there is no literature on health risk assessment of internal exposure. In view of this, an analytical method based on quaternary amine-functionalized core-shell-shell magnetic polymers (QA-CSS-MPs) was developed for the determination of seven metabolites in urine by MSPE-UPLC-DAD-HRMS. Furthermore, an improved QuEChERS method for the extraction of seven metabolites from human urine samples was introduced for the first time and satisfactory extraction rates were achieved. In addition, QA-CSS-MPs microspheres with core-shell-shell structure were designed and synthesized, and the morphology, composition and magnetic properties of the materials were fully characterized to verify the rationality of the synthetic route. Subsequently, QA-CSS-MPs microspheres were used as magnetic solid-phase extraction (MSPE) adsorbents for the purification of urine extracts, and UPLC-DAD-HRMS was used for the detection of seven metabolites. As a result, this method allows the accurate determination of seven metabolites in urine samples over an ultra-wide concentration range (0.001-100 mg/L). Under optimal experimental conditions, i.e., 2% hydrochloric acid in urine for the hydrolysis and 20 mg of QA-CSS-MPs for 5 min purification, the spiked recoveries of the seven target metabolites ranged from 81.5% to 117.7% with RSDs of 1.0%-9.4%. The limits of detection (LODs, S/N≥3) for the established method were in the range of 0.2-0.3 µg/L. The developed method was applied to 254 human urine samples for the determination of seven metabolites. The results showed that the concentration distributions of three xylene metabolites in urine, 2-MHA, 3-MHA, 4-MHA and total MHA, showed statistically significant differences for occupational exposure (p<0.001). In addition, the results of the internal exposure assessment showed that there is a high potential health risk associated with occupational exposure processes.

Assessment of urinary aromatic amines in Brazilian pregnant women and association with DNA damage: Influence of genetic diversity, lifestyle, and environmental and socioeconomic factors.

Aromatic amines (AAs) are polar organic chemicals with a wide environmental distribution originating from various sources, such as tobacco smoke, diesel exhaust, and dermal absorption from textile products with azo dyes. The toxicity profile of AAs is directly related to the amino group's metabolic activation and the generation of the reactive intermediate, forming DNA adducts and potential carcinogenicity. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) are an important biomarker of DNA damage. Since AAs have been shown to cross the placental barrier, being a risk factor for adverse birth outcomes, prenatal exposure is a great public health concern. The present study aimed to measure the urinary levels of 58 AAs in Brazilian pregnant women (n = 300) and investigated the impact of this exposure on DNA damage by quantifying 8OHdG levels. The influence of tobacco smoke exposure and dermal absorption of AAs by clothes on urinary levels was also assessed. The results showed a 100% detection rate for eight AAs, two of them regulated by the European Union (2,6-dimethylaniline and 2,4-diaminotolune). Hundreds of AAs may be derived from aniline, which here showed a median of 1.38 ng/mL. Aniline also correlated positively with 2,6-dimethylaniline, p-aminophenol, and other AAs, suggesting exposure to multiple sources. The present findings suggest that both tobacco smoke and dermal contact with clothes containing azo dyes are potential sources that might strongly influence urinary levels of AAs in Brazilian pregnant women. A multiple regression linear model (R2 = 0.772) suggested that some regulated AAs (i.e., 2-naphthylamine and 4-aminobiphenyl), nicotine, smoke habit, age, and Brazilian region could induce DNA damage occurrence, increasing the levels of 8OHdG. Given the limited available data on human exposure to carcinogenic AAs, as well as the lack of toxicological information on those non-regulated, further studies focused on measuring their levels in human fluids and the potential exposure sources are clearly essential.

Assessment of physicochemical properties of sorbent materials in passive and active sampling systems towards gaseous nitrogen-containing compounds.

The adsorption and desorption behavior of volatile nitrogen-containing compounds in vapor phase by solid-phase microextraction Arrow (SPME-Arrow) and in-tube extraction (ITEX) sampling systems, were investigated experimentally using gas chromatography-mass spectrometry. Three different SPME-Arrow coating materials, DVB/PDMS, MCM-41, and MCM-41-TP and two ITEX adsorbents, TENAX-GR and MCM-41-TP were compared to clarify the selectivity of the sorbents towards nitrogen-containing compounds. In addition, saturated vapor pressures for these compounds were estimated, both experimentally and theoretically. In this study, the adsorption of nitrogen-containing compounds on various adsorbents followed the Elovich model well, while a pseudo-first-order kinetics model best described the desorption kinetics. Pore volume and pore sizes of the coating sorbents were essential parameters for the determination of the adsorption performance for the SPME-Arrow sampling system. MCM-41-TP coating with the smallest pore size gave the slowest adsorption rate compared to that of DVB/PDMS and MCM-41 in the SPME-Arrow sampling system. Both adsorbent and adsorbate properties, such as hydrophobicity and basicity, affected the adsorption and desorption kinetics in SPME-Arrow system. The adsorption and desorption rates of studied C6H15N isomers in the MCM-41 and MCM-41-TP sorbent materials of SPME-Arrow system were higher for dipropylamine and triethylamine (branched amines) than for hexylamine (linear chain amines). DVB/PDMS-SPME-Arrow gave fast adsorption rates for the aromatic-ringed pyridine and o-toluidine. All studied nitrogen-containing compounds demonstrated high desorption rates with DVB/PDMS-SPME-Arrow. Chemisorption and physisorption were the sorption mechanisms in MCM-41- and MCM-41-TP- SPME-Arrow, but additional experiments are needed to confirm this. An active sampling technique ITEX gave comparable adsorption and desorption rates on the selective MCM-41-TP and universal TENAX-GR sorbent materials for all the compounds studied. Vapor pressures of nitrogen-containing compounds were experimentally estimated by using retention index approach and these values were compared with the theoretical ones, calculated using the COnductor-like Screening MOdel for Real Solvent (COSMO-RS) model. Both values agreed well with those found in the literature proving that these methods can be successfully used in predicting VOC's vapor pressures, e.g. for the formation of secondary organic aerosols.

Assessment of cellular responses in three-dimensional cell cultures through chemical exchange saturation transfer and 1 H MRS.

The article from this special issue was previously published in NMR In Biomedicine , Volume 35, Issue 9, 2022. For completeness we are including the title page of the article below. The full text of the article can be read in Issue 35:9 on Wiley Online Library: https://doi.org/10.1002/nbm.4757.

Non-regulated aromatic amines in clothing purchased in Spain and Brazil: Screening-level exposure and health impact assessment.

The staggering amount of chemicals in clothes and their harmful effects on human health and the environment have attracted the attention of regulatory agencies and the scientific community worldwide. Azo dyes are synthetic dyestuffs with widespread use in textile industries, currently classified as emerging pollutants of great health concern to consumers. These compounds may release one or more aromatic amines (AAs) after reductive cleavage of their azo bounds. Twenty-two AAs have already been regulated due to their carcinogenic effects. However, since information on their potential toxicity is not currently available, several AAs have not been still regulated by the European Union. Considering this gap, the present study aimed to assess the levels of forty non-regulated AAs in 240 clothing items from Spain and Brazil. The potential impact on the health of vulnerable population groups after dermal exposure to those garments was also evaluated. In Brazil, at least one AA was detected in the clothes, while in samples obtained in Spain, only two of them showed values below the limit of detection for AAs. In 75 clothes, at least one of the measured AAs was higher than the hazardous threshold (30 mg/kg), which can mean risks to human health since these compounds are suspected to be mutagenic. Aniline, the most common AA, showed a high detection rate (82%) in clothes, with significantly higher concentrations in items commercialized in Brazil (0.35 vs. 0.17 mg/kg; p = 0.032). Moreover, o-aminobenzenesulfonic and p-phenylenediamine, suspected mutagenic, were found at relevant concentrations in several clothes, mainly made of synthetic fibers. In this study, the hazard index associated with exposure to AAs through clothing was low (0.006-0.13) for all the population groups of both countries in the medium-bound scenario. However, its value was close to 1 for Brazilian pregnant women (0.998) when the maximum concentration value was considered under an upper-bound scenario. The risk of exposure to non-regulated AAs may be underestimated since only dermal exposure was considered for risk assessment. Moreover, the co-occurrence of other carcinogenic and non-carcinogenic substances present in skin-contact clothes should mean an additional source of potential risk.

Synthesis of chitosan succinate-g-amine functionalized mesoporous silica: Inorganic-organic nanohybrid for antibacterial assessment, antioxidant activity and pH-controlled drug delivery.

An innovative and proficient inorganic-organic nanohybrid was synthesized by using amine modified MCM-41 as an inorganic precursor combined with organic moiety, a derivative of chitosan i.e. chitosan succinate through amide bond. These nanohybrids can be used in diverse applications due to potential combination of desired properties of inorganic and organic components. The nanohybrid was characterized by FTIR, TGA, small angle powder XRD, zeta potential, particle size distribution, BET, proton NMR and 13C NMR techniques to confirm its formation. The synthesized hybrid was loaded with curcumin drug to check its potential application for controlled drug release, showing 80 % drug release in acidic medium (i.e. pH -5.0), while physiological pH -7.4 shows only 25 % release. The encapsulation efficiency of nanohybrid is 87.24 %. The results of antibacterial performances are demonstrated in terms of ZOI (zone of inhibition) which depicts that hybrid material shows better ZOI in gram negative (E. coli) than for gram positive (B. subtilis) bacteria. Nanohybrid was also tested for the antioxidant activity by using two different methods (DPPH and ABTS) radical scavenging methods. The ability of nano-hybrid to scavenge DPPH radicals was found 65 %, and ability to scavenge ABTS radicals was 62.47 %.

Screening of regulated aromatic amines in clothing marketed in Brazil and Spain: Assessment of human health risks.

Azo dyes used in textile products contain aromatic amines (AAs), which may be released into the environment after skin bacteria cleavage the azo bond. In Europe, 22 carcinogenic AAs are regulated. Unfortunately, no information is available in many non-European countries, including Brazil. This study aimed to determine the concentrations of 20 regulated AAs in clothes marketed in Brazil and Spain. Generally, higher levels of regulated AAs were found in samples sold in Brazil than in Spain, which is linked to the lack of regulation. Sixteen AAs showed concentrations above 5 mg/kg in samples commercialized in Brazil, while 11 exceeded that threshold in Spain. Regulated AAs with levels above 5 mg/kg were more found in synthetic clothes of pink color. Concentrations in clothing were also used to evaluate the dermal exposure to AAs in 3 vulnerable population groups. The highest exposure corresponded to 2,4-diaminoanisole for toddlers in Brazil and 4,4-oxydianiline for newborns in Spain. Non-cancer risks associated with exposure to 4,4-benzidine by Brazilian toddlers was 14.5 (above the threshold). On the other hand, 3,3-dichlorobenzidine was associated with potential cancer risks for newborns and toddlers in Brazil. Given this topic's importance, we recommend conducting continuous studies to determine the co-occurrence of carcinogenic substances.

A sensitive and economical method for simultaneous determination of D/L- amino acids profile in foods by HPLC-UV: Application in fermented and unfermented foods discrimination.

This work described a sensitive and economical HPLC-UV method with FDAA derivatization to simultaneously detect 36 D/l-amino acids, which provides higher sensitivity and lower cost than other HPLC-based methods. It was validated for linearity range (8-1000 µmol/L), limits of detection (2.68-62.44 pmol/L), limits of quantification (2.93 to 208.13 pmol/L), intraday precision (0.30 % - 5.31 %), interday precision (1.96 % - 8.04 %) and accuracy (86.53 % - 121.46 %). This method was then applied in the determination of D/L- amino acids abundance in fermented and unfermented food materials and showed the characteristics of each type of foods. The method also demonstrated good performance in another application case for the discrimination of different types of food materials based on D/L- amino acids profile. It emphasizes the ability of the method to study the characteristics, distribution and abundance of d-amino acids in foods and their potential application in food quality control.

Energy, exergy, economic, environment, exergo-environment based assessment of amine-based hybrid solvents for natural gas sweetening.

Natural gas is the cleanest form of fossil fuel that needs to be purified from CO2 and H2S to diminish harmful emissions and provide feasible processing. The conventional chemical and physical solvents used for this purpose have many drawbacks, including corrosion, solvent loss, high energy requirement, and the formation of toxic compounds, which ultimately disrupt the process and affect the environment. Hybrid solvents have lately been researched to cater to these liabilities and enhance process economics. This study screened eight solvents based on CO2 selectivity viscosity, absorption enthalpy, corrosivity, working capacity, specific heat, and vapor pressure. From the screened solvents, ten cases of hybrid solvents are simulated and optimized on Aspen HYSYS®. Furthermore, 5Es (Energy, Exergy, Economic, Environmental, and Exergy-environmental) analyses were performed on optimized cases, and results were compared with the base case, MEA (30 wt%). The hybrid blend of Sulfolane and MDEA with weight percentages of 6% and 24%, respectively, showed the highest energy savings of 20% concerning the base case. In addition, it offered 93% savings in exergy destruction and 17.26% in the total operating cost of the process. It is also promising to the environment due to reduced entropy sent to the ecosystem and controlled CO2 emissions. Therefore, the blend of Sulfolane and MDEA is proposed to Supersede the conventional solvent MEA for the natural gas sweetening process.

Fast and Cost-Efficient 17 O-Isotopic Labeling of Carboxylic Groups in Biomolecules: From Free Amino Acids to Peptide Chains.

17 O NMR spectroscopy is a powerful technique, which can provide unique information regarding the structure and reactivity of biomolecules. However, the low natural abundance of 17 O (0.04 %) generally requires working with enriched samples, which are not easily accessible. Here, we present simple, fast and cost-efficient 17 O-enrichment strategies for amino acids and peptides by using mechanochemistry. First, five unprotected amino acids were enriched under ambient conditions, consuming only microliter amounts of costly labeled water, and producing pure molecules with enrichment levels up to ∼40 %, yields ∼60-85 %, and no loss of optical purity. Subsequently, 17 O-enriched Fmoc/tBu-protected amino acids were produced on a 1 g/day scale with high enrichment levels. Lastly, a site-selective 17 O-labeling of carboxylic functions in peptide side-chains was achieved for RGD and GRGDS peptides, with ∼28 % enrichment level. For all molecules, 17 O ssNMR spectra were recorded at 14.1 T in reasonable times, making this an important step forward for future NMR studies of biomolecules.

Assessment of heterocyclic aromatic amines contents in flamed and braised chicken in Burkina Faso.

The nutritional status of meat is tarnished by its association with the induced cooking contaminants. The aim of this study was to assess the heterocyclic aromatic amines profile and contents in processed chicken in Burkina Faso. Eight polar and apolar heterocyclic aromatic amines (HAAs) including 2-mino-3-methylimidazo[4,5-f]quinolone (IQ), 3-amino-1,4-dimethyl-5H-pyrido[4, 3-b]indole (Trp-P1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P2), 2-mino-9H-pyrido-[2,3-b]indole (AαC), 2-amino-1-methyl-6-phenylimidazo[4, 5- ]pyridine (PhIP), 2-amino-3-methyl-9H-pyrido[2,3-b] indole (MeAαC), 2-amino-3,4,8-rimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) and 2-amino-3,8-imethylimidazo[4,5-]quinoxaline (MeIQx) were screened by high performance liquid chromatography from 29 samples of flamed chicken and 66 samples of braised chicken collected in Ouagadougou city. Apolar HAAs and polar HAAs were respectively 12 and 3 times more abundant in flamed chickens (32.66±10 and 3.48±10.39 ng/g, respectively) than in braised chickens (2.70±9.67 and 0.92 ng/g, respectively). The maximum levels of AαC were in the same proportions in flamed (12.01 ng/g) and braised chickens (14.13 ng/g). Flamed chicken had the highest Trp-P1 content (530.31 ng/g). The 4,8-DiMeIQx was not detected in braised chicken. The AαCs were more abundant in flamed than in braised chicken. The profile and the contents of the HAAs in processed chicken are related to cooking methods. Because of the high variability observed on the obtained concentrations, investigations on the contents of precursors in raw chicken, the effect of marinating ingredients on the formation of HAAs are needed.

Cheminformatics analysis of chemicals that increase estrogen and progesterone synthesis for a breast cancer hazard assessment.

Factors that increase estrogen or progesterone (P4) action are well-established as increasing breast cancer risk, and many first-line treatments to prevent breast cancer recurrence work by blocking estrogen synthesis or action. In previous work, using data from an in vitro steroidogenesis assay developed for the U.S. Environmental Protection Agency (EPA) ToxCast program, we identified 182 chemicals that increased estradiol (E2up) and 185 that increased progesterone (P4up) in human H295R adrenocortical carcinoma cells, an OECD validated assay for steroidogenesis. Chemicals known to induce mammary effects in vivo were very likely to increase E2 or P4 synthesis, further supporting the importance of these pathways for breast cancer. To identify additional chemical exposures that may increase breast cancer risk through E2 or P4 steroidogenesis, we developed a cheminformatics approach to identify structural features associated with these activities and to predict other E2 or P4 steroidogens from their chemical structures. First, we used molecular descriptors and physicochemical properties to cluster the 2,012 chemicals screened in the steroidogenesis assay using a self-organizing map (SOM). Structural features such as triazine, phenol, or more broadly benzene ramified with halide, amine or alcohol, are enriched for E2 or P4up chemicals. Among E2up chemicals, phenol and benzenone are found as significant substructures, along with nitrogen-containing biphenyls. For P4up chemicals, phenol and complex aromatic systems ramified with oxygen-based groups such as flavone or phenolphthalein are significant substructures. Chemicals that are active for both E2up and P4up are enriched with substructures such as dihydroxy phosphanedithione or are small chemicals that contain one benzene ramified with chlorine, alcohol, methyl or primary amine. These results are confirmed with a chemotype ToxPrint analysis. Then, we used machine learning and artificial intelligence algorithms to develop and validate predictive classification QSAR models for E2up and P4up chemicals. These models gave reasonable external prediction performances (balanced accuracy ~ 0.8 and Matthews Coefficient Correlation ~ 0.5) on an external validation. The QSAR models were enriched by adding a confidence score that considers the chemical applicability domain and a ToxPrint assessment of the chemical. This profiling and these models may be useful to direct future testing and risk assessments for chemicals related to breast cancer and other hormonally-mediated outcomes.

Polydiketoenamines for a Circular Plastics Economy.

The mismanagement and leakage of plastic waste into the environment are failures of modern society. Once in the environment, plastic waste degrades into microplastics on a time scale dependent on the resin chemistry and the associated biotic or abiotic process. The high surface area of microplastics results in the contamination of ecosystems through the leaching of toxic chemicals compounded with plastics during manufacturing. In addition, the small size of microplastics increases the likelihood that they will be inhaled or ingested, which has led to the bioaccumulation of microplastics with documented harm. Furthermore, microplastics are more readily aerosolized and distributed by weather systems to areas remote from locations where plastic waste has been mismanaged. Consequently, the carbon cycle must now account for plastic waste discharge, degradation, and dispersal in the environment after the end of useful life on a global scale.Circularity in plastics recycling endeavors to solve the waste problem while promoting greater sustainability. Circularity can be conducted at different stages in the plastics life cycle. Post-industrial recycling enabling scrap recovery in manufacturing is desirable for industrial material efficiency. However, the degradation of polymer chains currently limits the extent to which scrap recovery may be practiced repeatedly on the same material, particularly when the conversion of secondary resin to various plastic products is intolerant to deviations in polymer properties. Post-consumer recycling, on the other hand, is desirable for erasing the manufacturing history and use history of plastic-containing products. Post-consumer recycling involves cleaning and sorting plastic waste into bales, followed by mechanical recycling to produce dense feedstocks for downstream chemical processes required for deconstruction, monomer refinement, and secondary resin production. The efficiency and intensity of chemical processes used to recover reusable monomers or polymers remain low for most plastics. Consequently, there is an urgent need for novel polymers with useful or advantageous properties designed for recycling by addressing the challenges of resource recovery for reuse.In this Account, I discuss the design, discovery, and development of circular plastics based on the chemistry of polydiketoenamines. The diketoenamine bond provides a vantage point for the creation of thermoplastics, elastomers, and thermosets from polytopic triketone and amine monomers. The dynamic covalent character of the diketoenamine bond can be exploited during scrap recovery to provide resilience during mechanical recycling, maintaining baseline properties of the primary resin through multiple cycles of reuse. Furthermore, the hydrolyzability of the diketoenamine bond in strong acid can be exploited for efficient monomer recovery during chemical recycling. A systems-level analysis of polydiketoenamine circularity reveals substantive benefits in low-carbon manufacturing as well as a context to quantify the market potential, identifying use cases where circularity might be most effective. Leveraging these insights, it is possible to guide the process chemistry development necessary to scale monomer and resin production to meet imminent needs for more circular plastics in the market. These insights also provide a glimpse into the underlying molecular mechanisms critical to circularity in a new plastics economy while firmly establishing a role for creativity in polymer chemistry to provide innovative solutions.

Closed-Loop Recycling of Poly(Imine-Carbonate) Derived from Plastic Waste and Bio-based Resources.

Closed-loop recycling of polymers represents the key technology to convert plastic waste in a sustainable fashion. Efficient chemical recycling and upcycling strategies are thus highly sought-after to establish a circular plastic economy. Here, we present the selective chemical depolymerization of polycarbonate by employing a vanillin derivative as bio-based feedstock. The resulting di-vanillin carbonate monomer was used in combination with various amines to construct a library of reprocessable poly(imine-carbonate)s, which show tailor-made thermal and mechanical properties. These novel poly(imine-carbonate)s exhibit excellent recyclability under acidic and energy-efficient conditions. This allows the recovery of monomers in high yields and purity for immediate reuse, even when mixed with various commodity plastics. This work provides exciting new insights in the design of bio-based circular polymers produced by upcycling of plastic waste with minimal environmental impact.