Bioinspired and Bioderived Aqueous Electrocatalysis.

The development of efficient and sustainable electrochemical systems able to provide clean-energy fuels and chemicals is one of the main current challenges of materials science and engineering. Over the last decades, significant advances have been made in the development of robust electrocatalysts for different reactions, with fundamental insights from both computational and experimental work. Some of the most promising systems in the literature are based on expensive and scarce platinum-group metals; however, natural enzymes show the highest per-site catalytic activities, while their active sites are based exclusively on earth-abundant metals. Additionally, natural biomass provides a valuable feedstock for producing advanced carbonaceous materials with porous hierarchical structures. Utilizing resources and design inspiration from nature can help create more sustainable and cost-effective strategies for manufacturing cost-effective, sustainable, and robust electrochemical materials and devices. This review spans from materials to device engineering; we initially discuss the design of carbon-based materials with bioinspired features (such as enzyme active sites), the utilization of biomass resources to construct tailored carbon materials, and their activity in aqueous electrocatalysis for water splitting, oxygen reduction, and CO2 reduction. We then delve in the applicability of bioinspired features in electrochemical devices, such as the engineering of bioinspired mass transport and electrode interfaces. Finally, we address remaining challenges, such as the stability of bioinspired active sites or the activity of metal-free carbon materials, and discuss new potential research directions that can open the gates to the implementation of bioinspired sustainable materials in electrochemical devices.

NP-MRD: the Natural Products Magnetic Resonance Database.

The Natural Products Magnetic Resonance Database (NP-MRD) is a comprehensive, freely available electronic resource for the deposition, distribution, searching and retrieval of nuclear magnetic resonance (NMR) data on natural products, metabolites and other biologically derived chemicals. NMR spectroscopy has long been viewed as the 'gold standard' for the structure determination of novel natural products and novel metabolites. NMR is also widely used in natural product dereplication and the characterization of biofluid mixtures (metabolomics). All of these NMR applications require large collections of high quality, well-annotated, referential NMR spectra of pure compounds. Unfortunately, referential NMR spectral collections for natural products are quite limited. It is because of the critical need for dedicated, open access natural product NMR resources that the NP-MRD was funded by the National Institute of Health (NIH). Since its launch in 2020, the NP-MRD has grown quickly to become the world's largest repository for NMR data on natural products and other biological substances. It currently contains both structural and NMR data for nearly 41,000 natural product compounds from >7400 different living species. All structural, spectroscopic and descriptive data in the NP-MRD is interactively viewable, searchable and fully downloadable in multiple formats. Extensive hyperlinks to other databases of relevance are also provided. The NP-MRD also supports community deposition of NMR assignments and NMR spectra (1D and 2D) of natural products and related meta-data. The deposition system performs extensive data enrichment, automated data format conversion and spectral/assignment evaluation. Details of these database features, how they are implemented and plans for future upgrades are also provided. The NP-MRD is available at https://np-mrd.org.

Bisphenol A and bisphenol S disruptions of the mouse placenta and potential effects on the placenta-brain axis.

Placental trophoblast cells are potentially at risk from circulating endocrine-disrupting chemicals, such as bisphenol A (BPA). To understand how BPA and the reputedly more inert bisphenol S (BPS) affect the placenta, C57BL6J mouse dams were fed 200 µg/kg body weight BPA or BPS daily for 2 wk and then bred. They continued to receive these chemicals until embryonic day 12.5, whereupon placental samples were collected and compared with unexposed controls. BPA and BPS altered the expression of an identical set of 13 genes. Both exposures led to a decrease in the area occupied by spongiotrophoblast relative to trophoblast giant cells (GCs) within the junctional zone, markedly reduced placental serotonin (5-HT) concentrations, and lowered 5-HT GC immunoreactivity. Concentrations of dopamine and 5-hydroxyindoleacetic acid, the main metabolite of serotonin, were increased. GC dopamine immunoreactivity was increased in BPA- and BPS-exposed placentas. A strong positive correlation between 5-HT+ GCs and reductions in spongiotrophoblast to GC area suggests that this neurotransmitter is essential for maintaining cells within the junctional zone. In contrast, a negative correlation existed between dopamine+ GCs and reductions in spongiotrophoblast to GC area ratio. These outcomes lead to the following conclusions. First, BPS exposure causes almost identical placental effects as BPA. Second, a major target of BPA/BPS is either spongiotrophoblast or GCs within the junctional zone. Third, imbalances in neurotransmitter-positive GCs and an observed decrease in docosahexaenoic acid and estradiol, also occurring in response to BPA/BPS exposure, likely affect the placental-brain axis of the developing mouse fetus.

Anisotropic Near-Zero Thermal Expansion in REAg xGa4- x ( RE = La-Nd, Sm, Eu, and Yb) Induced by Structural Reorganization.

In this work, we have discovered the anisotropic near-zero thermal expansion (NZTE) behavior in a family of compounds REAg xGa4- x ( RE = La-Nd, Sm, Eu, and Yb). The compounds adopt the CeAl2Ga2 structure type and were obtained as single crystals in high yield by metal flux growth technique using gallium as active flux. Temperature-dependent single crystal X-ray diffraction suggests that all the compounds exhibit near zero thermal expansion along c direction in the temperature range of 100-450 K. Temperature-dependent X-ray absorption near-edge spectroscopic study confirmed ZTE behavior is due to the geometrical features associated within the crystal structure. The anisotropic NZTE behavior was further established by anisotropic magnetic measurements on selected single crystals. The atomic displacement parameters, apparent bond lengths, bond angles, and structural distortion with respect to the temperature reveal that geometric features associated with the structural distortion cause the anisotropic NZTE along c-direction. The preliminary magnetic studies suggest all the compounds are paramagnetic at room temperature except LaAgGa3. Electrical resistivity study reveals that compounds from this series are metallic in nature.

A Trimodal Closomer Drug-Delivery System Tailored with Tracing and Targeting Capabilities.

The construction and application of a unique monodisperse closomer drug-delivery system (CDDS) integrating three different functionalities onto an icosahedral closo-dodecaborane [B12 ](2-) scaffold is described. Eleven B-OH vertices of [closo-B12 (OH)12 ](2-) were used to attach eleven copies of the anticancer drug chlorambucil and the targeting vector glucosamine through a bifurcating lysine linker. The remaining twelfth vertex was used to attach a fluorescent imaging probe. The presence of multiple glucosamine units offered a monodisperse and highly water-soluble CDDS with a high payload of therapeutic cargo. This array enhanced the penetration of the drug into cancer cells by exploiting the overexpression of GLUT-1 receptors present on cancer cells. About 15-fold enhancement in cytotoxicity was observed for CDDS-1 against Jurkat cells, compared to CDDS-2, which lacks the GLUT-1 targeting glucosamine. A cytotoxicity comparison of CDDS-1 against colorectal RKO cells and its GLUT-1 knock-out version confirmed that GLUT-1 mediates endocytosis. Using fluorescent markers both CDDS-1 and -2 were traced to the mitochondria, a novel target for alkylating agents.

Metal Flux Growth, Structural Relations, and Physical Properties of EuCu2Ge2 and Eu3T2In9 (T = Cu and Ag).

Single crystals (SCs) of the compounds Eu3Ag2In9 and EuCu2Ge2 were synthesized through the reactions run in liquid indium. Eu3Ag2In9 crystallizes in the La3Al11 structure type [orthorhombic space group (SG) Immm] with the lattice parameters: a = 4.8370(1) Å, b = 10.6078(3) Å, and c = 13.9195(4) Å. EuCu2Ge2 crystallizes in the tetragonal ThCr2Si2 structure type (SG I4/mmm) with the lattice parameters: a = b = 4.2218(1) Å, and c = 10.3394(5) Å. The crystal structure of Eu3Ag2In9 is comprised of edge-shared hexagonal rings consisting of indium. The one-dimensional chains of In6 rings are shared through the edges, which are further interconnected with other six-membered rings forming a three-dimensional (3D) stable crystal structure along the bc plane. The crystal structure of EuCu2Ge2 can be explained as the complex [CuGe](2+δ)- polyanionic network embedded with Eu ions. These polyanionic networks present in the crystal structure of EuCu2Ge2 are shared through the edges of the 011 plane containing Cu and Ge atoms, resulting in a 3D network. The structural relationship between Eu3T2In9 and EuCu2Ge2 has been discussed in detail, and we conclude that Eu3T2In9 is the metal deficient variant of EuCu2Ge2. The magnetic susceptibilities of Eu3T2In9 (T = Cu and Ag) and EuCu2Ge2 were measured between 2 and 300 K. In all cases, magnetic susceptibility data followed Curie-Weiss law above 150 K. Magnetic moment values obtained from the measurements indicate the probable mixed/intermediate valent behavior of the europium atoms, which was further confirmed by X-ray absorption studies and bond distances around the Eu atoms. Electrical resistivity measurements suggest that Eu3T2In9 and EuCu2Ge2 are metallic in nature.

Cooperative Copper Single-Atom Catalyst in 2D Carbon Nitride for Enhanced CO2 Electrolysis to Methane.

Renewable-electricity-powered carbon dioxide (CO2) reduction (eCO2R) to high-value fuels like methane (CH4) holds the potential to close the carbon cycle at meaningful scales. However, this kinetically staggered 8-electron multistep reduction suffers from inadequate catalytic efficiency and current density. Atomic Cu-structures can boost eCO2R-to-CH4 selectivity due to enhanced intermediate binding energies (BEs) resulting from favorably shifted d-band centers. In this work, 2D carbon nitride (CN) matrices, viz. Na-polyheptazine (PHI) and Li-polytriazine imides (PTI), are exploited to host Cu-N2 type single-atom sites with high density (≈1.5 at%), via a facile metal-ion exchange process. Optimized Cu loading in nanocrystalline Cu-PTI maximizes eCO2R-to-CH4 performance with Faradaic efficiency (FECH4) of ≈68% and a high partial current density of 348 mA cm-2 at -0.84 V vs reversible hydrogen electrode (RHE), surpassing the state-of-the-art catalysts. Multi-Cu substituted N-appended nanopores in the CN frameworks yield thermodynamically stable quasi-dual/triple sites with large interatomic distances dictated by the pore dimensions. First-principles calculations elucidate the relative Cu-CN cooperative effects between the matrices and how the Cu local environment dictates the adsorbate BEs, density of states, and CO2-to-CH4 energy profile landscape. The 9N pores in Cu-PTI yield cooperative Cu-Cu sites that synergistically enhance the kinetics of the rate-limiting steps in the eCO2R-to-CH4 pathway.

cRGD peptide-conjugated icosahedral closo-B12(2-) core carrying multiple Gd3+-DOTA chelates for α(v)ß3 integrin-targeted tumor imaging (MRI).

A vertex-differentiated icosahedral closo-B(12)(2-) core was utilized to construct a α(v)ß(3) integrin receptor-targeted (via cRGD peptide) high payload MRI contrast agent (CA-12) carrying 11 copies of Gd(3+)-DOTA chelates attached to the closo-B(12)(2-) surface via suitable linkers. The resulting polyfunctional MRI contrast agent possessed a higher relaxivity value per-Gd compared to Omniscan, a small molecular contrast agent commonly used in clinical settings. The α(v)ß(3) integrin receptor specificity of CA-12 was confirmed via in vitro cellular binding experiments and in vivo MRI of mice bearing human PC-3 prostate cancer xenografts. Integrin α(v)ß(3)-positive MDA-MB-231 cells exhibited 300% higher uptake of CA-12 than α(v)ß(3)-negative T47D cells. Serial T1-weighted MRI showed superior contrast enhancement of tumors by CA-12 compared to both a nontargeted 12-fold Gd(3+)-DOTA closomer control (CA-7) and Omniscan. Contrast enhancement by CA-12 persisted for 4 h postinjection, and subsequent enhancement of kidney tissue indicated a renal elimination route similar to Omniscan. No toxic effects of CA-12 were apparent in any mice for up to 24 h postinjection. Post-mortem ICP-OES analysis at 24 h detected no residual Gd in any of the tissue samples analyzed.

Efficient synthesis of diverse heterobifunctionalized clickable oligo(ethylene glycol) linkers: potential applications in bioconjugation and targeted drug delivery.

Herein we describe the sequential synthesis of a variety of azide-alkyne click chemistry-compatible heterobifunctional oligo(ethylene glycol) (OEG) linkers for bioconjugation chemistry applications. Synthesis of these bioorthogonal linkers was accomplished through desymmetrization of OEGs by conversion of one of the hydroxyl groups to either an alkyne or azido functionality. The remaining distal hydroxyl group on the OEGs was activated by either a 4-nitrophenyl carbonate or a mesylate (-OMs) group. The -OMs functional group served as a useful precursor to form a variety of heterobifunctionalized OEG linkers containing different highly reactive end groups, e.g., iodo, -NH(2), -SH and maleimido, that were orthogonal to the alkyne or azido functional group. Also, the alkyne- and azide-terminated OEGs are useful for generating larger discrete poly(ethylene glycol) (PEG) linkers (e.g., PEG(16) and PEG(24)) by employing a Cu(I)-catalyzed 1,3-dipolar cycloaddition click reaction. The utility of these clickable heterobifunctional OEGs in bioconjugation chemistry was demonstrated by attachment of the integrin (α(v)ß(3)) receptor targeting peptide, cyclo-(Arg-Gly-Asp-D-Phe-Lys) (cRGfKD) and to the fluorescent probe sulfo-rhodamine B. The synthetic methodology presented herein is suitable for the large scale production of several novel heterobifunctionalized OEGs from readily available and inexpensive starting materials.

Unraveling the reaction mechanisms for furfural electroreduction on copper.

Electrochemical routes for the valorization of biomass-derived feedstock molecules offer sustainable pathways to produce chemicals and fuels. However, the underlying reaction mechanisms for their electrochemical conversion remain elusive. In particular, the exact role of proton-electron coupled transfer and electrocatalytic hydrogenation in the reaction mechanisms for biomass electroreduction are disputed. In this work, we study the reaction mechanism underlying the electroreduction of furfural, an important biomass-derived platform chemical, combining grand-canonical (constant-potential) density functional theory-based microkinetic simulations and pH dependent experiments on Cu under acidic conditions. Our simulations indicate the second PCET step in the reaction pathway to be the rate- and selectivity-determining step for the production of the two main products of furfural electroreduction on Cu, i.e., furfuryl alcohol and 2-methyl furan, at moderate overpotentials. We further identify the source of Cu's ability to produce both products with comparable activity in their nearly equal activation energies. Furthermore, our microkinetic simulations suggest that surface hydrogenation steps play a minor role in determining the overall activity of furfural electroreduction compared to PCET steps due to the low steady-state hydrogen coverage predicted under reaction conditions, the high activation barriers for surface hydrogenation and the observed pH dependence of the reaction. As a theoretical guideline, low pH (<1.5) and moderate potential (ca. -0.5 V vs. SHE) conditions are suggested for selective 2-MF production.

FeNC Oxygen Reduction Electrocatalyst with High Utilization Penta-Coordinated Sites.

Atomic Fe in N-doped carbon (FeNC) electrocatalysts for oxygen (O2 ) reduction at the cathode of proton exchange membrane fuel cells are the most promising alternative to platinum-group-metal catalysts. Despite recent progress on atomic FeNC O2  reduction, their controlled synthesis and stability for practical applications remain challenging. A two-step synthesis approach has recently led to significant advances in terms of Fe-loading and mass activity; however, the Fe utilization remains low owing to the difficulty of building scaffolds with sufficient porosity that electrochemically exposes the active sites. Herein, this issue is addressed by coordinating Fe in a highly porous nitrogen-doped carbon support (≈3295 m2  g-1 ), prepared by pyrolysis of inexpensive 2,4,6-triaminopyrimidine and a Mg2+ salt active site template and porogen. Upon Fe coordination, a high electrochemical active site density of 2.54 × 1019  sites gFeNC -1  and a record 52% FeNx electrochemical utilization based on in situ nitrite stripping are achieved. The Fe single atoms are characterized pre- and post-electrochemical accelerated stress testing by aberration-corrected high-angle annular dark field scanning transmission electron microscopy, showing no Fe clustering. Moreover, ex situ X-ray absorption spectroscopy and low-temperature Mössbauer spectroscopy suggest the presence of penta-coordinated Fe sites, which are further studied by density functional theory calculations.

Synthesis of vertex-differentiated icosahedral closo-boranes: polyfunctional scaffolds for targeted drug delivery.

We report methods for the synthesis of vertex-differentiated icosahedral closo-boranes. A single B-OH vertex of the icosahedral borane [closo-B(12)(OH)(12)](2-) was derivatized to prepare [closo-B(12)(OR)(OH)(11)](2-) using optimized alkylation conditions and purification procedures. Several representative vertex-differentiated icosahedral closo-boranes were prepared utilizing carbonate ester and azide-alkyne click chemistries on the surface of the closo-B(12)(2-) core.

Switchgrass Metabolomics Reveals Striking Genotypic and Developmental Differences in Specialized Metabolic Phenotypes.

Switchgrass (Panicum virgatum L.) is a bioenergy crop that grows productively on lands not suitable for food production and is an excellent target for low-pesticide input biomass production. We hypothesize that resistance to insect pests and microbial pathogens is influenced by low-molecular-weight compounds known as specialized metabolites. We employed untargeted liquid chromatography-mass spectrometry, quantitative gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance spectroscopy to identify differences in switchgrass ecotype metabolomes. This analysis revealed striking differences between upland and lowland switchgrass metabolomes as well as distinct developmental profiles. Terpenoid- and polyphenol-derived specialized metabolites were identified, including steroidal saponins, di- and sesqui-terpenoids, and flavonoids. The saponins are particularly abundant in switchgrass extracts and have diverse aglycone cores and sugar moieties. We report seven structurally distinct steroidal saponin classes with unique steroidal cores and glycosylated at one or two positions. Quantitative GC-MS revealed differences in total saponin concentrations in the leaf blade, leaf sheath, stem, rhizome, and root (2.3 ± 0.10, 0.5 ± 0.01, 2.5 ± 0.5, 3.0 ± 0.7, and 0.3 ± 0.01 µg/mg of dw, respectively). The quantitative data also demonstrated that saponin concentrations are higher in roots of lowland (ranging from 3.0 to 6.6 µg/mg of dw) than in upland (from 0.9 to 1.9 µg/mg of dw) ecotype plants, suggesting ecotypic-specific biosynthesis and/or biological functions. These results enable future testing of these specialized metabolites on biotic and abiotic stress tolerance and can provide information on the development of low-input bioenergy crops.

Metal coordination in C2N-like materials towards dual atom catalysts for oxygen reduction.

Single-atom catalysts, in particular the Fe-N-C family of materials, have emerged as a promising alternative to platinum group metals in fuel cells as catalysts for the oxygen reduction reaction. Numerous theoretical studies have suggested that dual atom catalysts can appreciably accelerate catalytic reactions; nevertheless, the synthesis of these materials is highly challenging owing to metal atom clustering and aggregation into nanoparticles during high temperature synthesis treatment. In this work, dual metal atom catalysts are prepared by controlled post synthetic metal-coordination in a C2N-like material. The configuration of the active sites was confirmed by means of X-ray adsorption spectroscopy and scanning transmission electron microscopy. During oxygen reduction, the catalyst exhibited an activity of 2.4 ± 0.3 A gcarbon -1 at 0.8 V versus a reversible hydrogen electrode in acidic media, comparable to the most active in the literature. This work provides a novel approach for the targeted synthesis of catalysts containing dual metal sites in electrocatalysis.

Photochemistry of 1,n-dibenzyloxy-9,10-anthraquinones.

The photochemistry of a series of 9,10-anthraquinones with multiple benzyloxy substituents was investigated. In polar solvent, the expected Blankespoor oxidative cleavage reaction is the major reaction pathway, but in most cases, several minor products were observed. In nonpolar solvents, the abundance of these minor products increases dramatically. Four types of product were observed with the favored reaction pathway shifting with minor changes in substitution on the anthraquinone. Several types of product require cleavage of the C-O bond on the benzyloxy group and, apparently, follow a photo-Claisen-type mechanism. Others involve the expected 1,5-diradical but do not exhibit the single-electron transfer usually observed in the Blankespoor-type reaction. The results indicate the importance of considering the medium and photoredox behavior in anthraquinone photochemistry.

Polyaniline Hybrid Nanofibers via Green Interfacial Polymerization for All-Solid-State Symmetric Supercapacitors.

In this study, we report an enormously simple green approach for the synthesis of polyaniline hybrid (PANI-SO) nanofibers in emeraldine salt form. We have carried out the synthesis via an interfacial polymerization method using vegetable oil as an organic phase instead of the commonly used solvents like CHCl3, CCl4, etc. Characterization techniques such as Fourier transform infrared (FTIR), UV-visible, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) have been used for studying the synthesized polyaniline hybrid nanofibers. An interesting observation is the crystallization of small organic molecules in the PANI matrix. PANI-SO shows a pseudocapacitance behavior with a capacitance value of 302 F g-1 at a current density of 1 A g-1. In addition, the material shows an energy density of 26.8 W h kg-1 and a maximum power density of 402.6 W kg-1. Furthermore, the PANI-SO electrode maintains about 84% of the initial capacitance after 1000 cycles. Similarly, the PANI-SO symmetric solid-state supercapacitor shows an areal capacitance of 118.7 mF cm-2 and retains a stability of 80% even after 1000 cycles. Thus, the PANI-SO electrode shows a good cyclic performance, which implies the structural stability of PANI-SO nanofibers. The electrochemical properties of PANI-SO are compared with those of PANI nanofibers synthesized by taking CHCl3 as the organic phase and keeping all other parameters identical. PANI-SO is observed to be a superior material compared to the latter one. All electrochemical analyses show that the PANI synthesized using cooking soyabean oil (PANI-SO) is an effective supercapacitor material.

Deconvolution of phase-size-strain effects in metal carbide nanocrystals for enhanced hydrogen evolution.

Understanding the descriptors of electrochemical activity and ways to modulate them are of paramount importance for the efficient structural engineering of electrocatalysts. Although, many studies separately elucidated the significance of thermodynamic and kinetic descriptors, lack of integrative approaches bars the potential utilization of these engineering tools for electrocatalytic activity enhancement. Here, through a facile post-carbonization synthetic technique using templated polyoxometalate based metal organic frameworks (POMOFs), we integrate three major structural engineering tools, viz. phase, size and strain into cost-effective Mo and W carbide electrocatalysts, and demonstrate how these factors qualitatively and quantitatively affect the critical descriptors of electrochemical activity. Deconvolution of these effects through combined experimental-theoretical analyses, shines new light on structure-activity relationships in this class of HER electrocatalysts. Optimum modulation of the structural tools culminated into the design of a superior electrocatalyst, consisting of ultrasmall γ-WC nanocrystals supported on N doped graphitic carbon that exhibited multifold activity enhancement in terms of onset potential, current density and Tafel slope compared to its structural analogues reported in this work and elsewhere. The present comprehensive study showcasing the effects of the structural engineering tools on activity will have considerable influence on future designs of more efficient nano-composite electrocatalysts.

Highly efficient bifunctional oxygen reduction/evolution activity of a non-precious nanocomposite derived from a tetrazine-COF.

We report a novel s-tetrazine based covalent organic framework (TZA-COF) and its hybrid nanocomposites with reduced graphene oxide (TZA-COF-rGO) and Co metal to illustrate novel structure-activity relationships in this class of compounds for electrocatalytic oxygen reduction reaction (ORR). The Co-impregnated hybrid composites (TZA-COF-rGO-Co) were further annealed to yield Co-encapsulated nitrogen doped graphitic carbon (Co@NC-600), which exhibited excellent ORR activity comparable to that of the state-of-the art Pt/C in terms of onset potential, E1/2 (half-wave potential), 4e- reduction selectivity and methanol tolerance. Sequential mechanistic analyses of activity enhancement and electron transfer pathways for the ORR, at different stages of controlled catalyst engineering, elucidated the crucial role of active sites and overall catalyst nature in tuning the ORR mechanism. Co@NC-600 also exhibited high oxygen evolution reaction (OER) activity under alkaline conditions which makes it one of the most efficient non-precious metal bifunctional catalysts, capable of catalyzing complex 4e- reduction processes like the ORR and OER.

Author Correction: Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood.

Xenoestrogens are chemicals found in plant products, such as genistein (GEN), and in industrial chemicals, e.g., bisphenol A (BPA), present in plastics and other products that are prevalent in the environment. Early exposure to such endocrine disrupting chemicals (EDC) may affect brain development by directly disrupting neural programming and/or through the microbiome-gut-brain axis. To test this hypothesis, California mice (Peromyscus californicus) offspring were exposed through the maternal diet to GEN (250 mg/kg feed weight) or BPA (5 mg/kg feed weight, low dose- LD or 50 mg/kg, upper dose-UD), and dams were placed on these diets two weeks prior to breeding, throughout gestation, and lactation. Various behaviors, gut microbiota, and fecal metabolome were assessed at 90 days of age. The LD but not UD of BPA exposure resulted in individuals spending more time engaging in repetitive behaviors. GEN exposed individuals were more likely to exhibit such behaviors and showed socio-communicative disturbances. BPA and GEN exposed females had increased number of metabolites involved in carbohydrate metabolism and synthesis. Males exposed to BPA or GEN showed alterations in lysine degradation and phenylalanine and tyrosine metabolism. Current findings indicate cause for concern that developmental exposure to BPA or GEN might affect the microbiome-gut-brain axis.