Reagents Research Articles

Carbon Dioxide as a Sustainable Reagent in Circular Hydrometallurgy.

This review highlights the use of CO2 as a reagent in hydrometallurgy, with emphasis on the new concept of circular hydrometallurgy. It is shown how waste CO2 can be utilised in hydrometallurgical operations for pH control or regeneration of acids for leaching. Metal-rich raffinate solutions generated after removal of the valuable metals can serve as feedstocks for mineral carbonation, providing alternative avenues for CO2 sequestration. Furthermore, CO2 can also be used as a renewable feedstock for the production of chemical reagents that can find applications in hydrometallurgy as lixiviant, as precipitation reagent or for pH control. Mineral carbonation can be combined with chemical reactions involving metal complexation reagents, as well as with solvent extraction processes for the concurrent precipitation of metal carbonates and acid regeneration. An outlook for future research in the area is also presented.

Choice of an environmentally friendly method of producing cellulose from flax biomass (<i>Linum usitatissimum linaceae</i>) grown in different regions of the Volga region

The experimental assessment of prospects of receiving cellulose material on the basis of use of vegetable raw materials – straw of a flax-dolgunetc is carried out. Results of researches showed a possibility of application for extraction of cellulose of the water solutions containing hydrogen peroxide, hydroxide and sodium bisulfite in the conditions of high-temperature influence within 2 hours with receiving the technical cellulose suitable for production of cardboard and packaging materials. For purification of technical cellulose, it was carried out additional processing by solution of hydrogen peroxide and acetic acid in similar parametrical conditions that allowed to receive a target product with high extent of maintenance of the main substance, at insignificant amount of the accompanying impurity. The presented results show a possibility of the solution of questions of environmental safety at the organization of process of receiving cellulose on the basis of renewable vegetable raw materials with use of the chemical reagents which are not containing compounds of sulfur.

Evaluation of allosteric NMDA receptor modulation by GluN2A-selective antagonists using pharmacological equilibrium modeling.

NMDA-type ionotropic glutamate receptors are critically involved in excitatory neurotransmission and their dysfunction is implicated in many brain disorders. Allosteric modulators with selectivity for specific NMDA receptor subtypes are therefore attractive as therapeutic agents, and sustained drug discovery efforts have resulted in a wide range of new allosteric modulators. However, evaluation of allosteric NMDA receptor modulators is limited by the lack of operational ligand-receptor models to describe modulator binding dissociation constants (KB) and effects on agonist binding affinity (α) and efficacy (β). Here, we describe a pharmacological equilibrium model that encapsulates activation and modulation of NMDA receptors, and we apply this model to afford deeper understanding of GluN2A-selective negative allosteric modulators (NAMs), TCN-201, MPX-004, and MPX-007. We exploit slow NAM unbinding to examine receptors at hemi-equilibrium when fully occupied by agonists and modulators to demonstrate that TCN-201 display weaker binding and negative modulation of glycine binding affinity (KB = 42 nM, α = 0.0032) compared to MPX-004 (KB = 9.3 nM, α = 0.0018) and MPX-007 (KB = 1.1 nM, α = 0.00053). MPX-004 increases agonist efficacy (β = 1.19), whereas TCN-201 (β = 0.76) and MPX-007 (β = 0.82) reduce agonist efficacy. These values describing allosteric modulation of diheteromeric GluN1/2A receptors with two modulator binding sites are unchanged in triheteromeric GluN1/2A/2B receptors with a single binding site. This evaluation of NMDA receptor modulation reveals differences between ligand analogs that shape their utility as pharmacological tool compounds and facilitates the design of new modulators with therapeutic potential. Significance Statement Detailed understanding of allosteric NMDA receptor modulation requires pharmacological methods to quantify modulator binding affinity and the strengths of modulation of agonist binding and efficacy. We describe a generic ligand-receptor model for allosteric NMDA receptor modulation and use this model for the characterization of GluN2A-selective NAMs. The model enables quantitative evaluation of a broad range of NMDA receptor modulators and provides opportunities to optimize these modulators by embellishing the interpretation of their structure-activity relationships.

Physical–Chemical–Biological Pretreatment for Biomass Degradation and Industrial Applications: A Review

Lignocellulosic biomass, including agricultural, forestry, and energy crop waste, is one of Earth’s most abundant renewable resources, accounting for approximately 50% of global renewable resources. It contains cellulose, hemicellulose, and lignin, making it crucial for biofuels and bio-based chemicals. Due to its complex structure, single-pretreatment methods are inefficient, leading to the development of combined pretreatment technologies. These methods enhance cellulose accessibility and conversion efficiency. This paper analyzes the principles, advantages, and disadvantages of various combined pretreatment methods and their practical benefits. It highlights recent research achievements and applications in biofuel, biochemical production, and feed. By integrating multiple pretreatment methods, biomass degradation efficiency can be significantly improved, energy consumption reduced, and chemical reagent use minimized. Future advancements in combined physical, chemical, and biological pretreatment technologies will further enhance biomass utilization efficiency, reduce energy consumption, and protect the environment, providing robust support for sustainable renewable energy development and ecological protection.

Time-resolved photoelectron spectroscopy at surfaces

Light is still an important spectroscopic tool for investigating the electronic structure of surfaces. Time-resolved photoelectron spectroscopy has mainly been developed in the last 30 years. It is therefore not surprising that the topic was hardly mentioned in the last issue on “The first thirty years” of surface science. In the second thirty years, however, we have seen tremendous progress in the development of time-resolved photoelectron spectroscopy on surfaces. Femtosecond light pulses and advanced photoelectron detection schemes are increasingly being used to study the electronic structure and dynamics of occupied and unoccupied electronic states and dynamic processes such as the energy and momentum relaxation of electrons, charge transfer at interfaces and collective processes such as plasmonic excitation and optical field screening. Using spin- and time-resolved photoelectron spectroscopy, we were able to study ultrafast spin dynamics, electron-magnon scattering and spin structures in magnetic and topological materials. Light also provides photon energy as well as electric and magnetic fields that can influence molecular surface processes to steer surface photochemistry and hot-electron-driven catalysis. In addition, we can consider light as a chemical reagent that can alter the properties of matter by creating non-equilibrium states and ultrafast phase transitions in correlated materials through the coupling of electrons, phonons and spins. Electric fields have also been used to temporarily change the electronic structure. This opened up new methods and areas such as high harmonic generation, light wave electronics and attosecond physics. This overview certainly cannot cover all these interesting topics. But also as a testimony to the cohesion and constructive exchange in our ultrafast community, a number of colleagues have come together to share their expertise and views on the very vital field of dynamics at surfaces. Following the introduction, the interested reader will find a list of contributions and a brief summary in Section 1.3.

Applicability of few layer graphene derived from annoni grass biomass on the mechanical properties of cement mortars

In this work, we report the potential applicability of few layer graphene (FLG) synthesized from annoni grass (AG) biomass (Eragrostis plana Nees) by investigating its impact on the flexural and compression strength of cement mortars. For this purpose the AG biomass was collected and burnt at the temperature of 400 °C per 60 min, obtaining the AG ash (AGA). For FLG production, the AGA was mixture with the chemical reagent potassium hydroxide (KOH) and burnt at the temperature and time of 850 °C and 60 min, respectively. For the mechanical properties analysis, a reference sample (A0-without FLG) and samples with different percentage of FLG were prepared, specifically 0.02 % (A1), 0.03 % (A2), 0.05 % (A3), 0.07 % (A4) and 0.1 % (A5). Statistical analysis (Analysis of Variance, ANOVA) of the mechanical properties demonstrates a maximum flexural and compression strength in sample A2. The flexural and compression strength increase 25.2 % and 10.1 % compared to the reference mortar. These results indicate that the FLG produced from AG not only improves the mechanical properties of mortars but also presents significant environmental benefits, because AG is considered an invasive pest of agricultural fields of the southern region of Brazil. Therefore, with its removal from the fields it would be contributing to environmental preservation.

Ultrasensitive Flexible Organic Synaptic Transistors Modulated by a Chemically Cross-Linked Solvent-Resistive Ion Composite.

We demonstrate a flexible organic synaptic transistor (FOST) with an ion-composite electrolyte film resistant to chemical reagents, which uses a three-dimensionally cross-linked polyimide matrix to accommodate a high-concentration ionic liquid. FOST shows versatile synaptic plasticity for classical conditioning, high-pass filtering, and the learning-forgetting process. The device achieves low-energy consumption down to 1.02 femtojoule per synaptic event with an ultrasensitive impulse to presynaptic spike down to 0.5 mV. Moreover, the electrical performance of the device is still stable after 1000 mechanical bending cycles. These results demonstrate that the device can be applied to future flexible neuromorphic electronics.

Aerobic Thiols Oxidative Coupling to Disulfides over Robust CoOx Nanoclusters Confined within Hierarchical Silicalite-1 Zeolite.

Disulfide is an important organic reagent and synthetic intermediate that is widely used in organic synthesis, polymers, and other fields, but its synthesis still suffers from many environmental pollution and economic problems. Here, we present an environmentally friendly and efficient base-free aerobic oxidative thiol coupling catalyzed by heterogeneous CoOx nanoclusters entrapped in hierarchical silicalite-1 zeolite, synthesized by combining silane pore expansion and metal coordination methods under hydrothermal conditions. It is confirmed that open hierarchical channels favor mass diffusion, and the chemical valence of Co species in CoOx/h-S-1-H is +2, which is different from that of Co3O4 particles in CoOx/h-S-1-I. CoOx nanoclusters, are strongly fixed in the channels of silicalite-1 zeolite via Co-O-Si bonds, which is of great importance for the high catalytic activity in both symmetrical and unsymmetrical oxidative thiol coupling reactions. After recycling experiments four times, the CoOx/h-S-1-H used has almost the same chemical state and the same distribution of Co(II) species as the fresh catalysts. Based on DFT calculations and inhibition experiments, the oxidative coupling of thiols undergoes a free radical mechanism in which Co(III) causes RS-H cleavage into RS· and H· species. Subsequently, two RS· radicals are coupled to disulfides, while H· radicals react with the O species to form H2O molecules. This work not only provides guidance on catalyst design and parameter optimization for oxidative thiol coupling but also advances the understanding of the aerobic oxidation mechanism.

Discovery and Characterization of BAY-184: A New Potent and Selective Acylsulfonamide-Benzofuran In Vivo-Active KAT6AB Inhibitor.

KAT6A and KAT6B genes are two closely related lysine acetyltransferases that transfer an acetyl group from acetyl coenzyme A (AcCoA) to lysine residues of target histone substrates, hence playing a key role in chromatin regulation. KAT6A and KAT6B genes are frequently amplified in various cancer types. In breast cancer, the 8p11-p12 amplicon occurs in 12-15% of cases, resulting in elevated copy numbers and expression levels of chromatin modifiers like KAT6A. Here, we report the discovery of a new acylsulfonamide-benzofuran series as a novel structural class for KAT6A/B inhibition. These compounds were identified through high-throughput screening and subsequently optimized using molecular modeling and cocrystal structure determination. The final tool compound, BAY-184 (29), was successfully validated in an in vivo proof-of-concept study.

The Discovery of MORF-627, a Highly Selective Conformationally-Biased Zwitterionic Integrin αvβ6 Inhibitor for Fibrosis.

Inhibition of integrin αvβ6 is a promising approach to the treatment of fibrotic disease such as idiopathic pulmonary fibrosis. Screening a small library combining head groups that stabilize the bent-closed conformation of integrin αIIbβ3 with αv integrin binding motifs resulted in the identification of hit compounds that bind the bent-closed conformation of αvβ6. Crystal structures of these compounds bound to αvβ6 and related integrins revealed opportunities to increase potency and selectivity, and these efforts were accelerated using accurate free energy perturbation (FEP+) calculations. Optimization of PK parameters including permeability, bioavailability, clearance, and half-life resulted in the discovery of development candidate MORF-627, a highly selective inhibitor of αvβ6 that stabilizes the bent-closed conformation and has good oral PK. Unfortunately, the compound showed toxicity in a 28-day NHP safety study, precluding further development. Nevertheless, MORF-627 is a useful tool compound for studying the biology of integrin αvβ6.

Discovery of Potent and Selective Blockers Targeting the Epilepsy-Associated KNa1.1 Channel.

Gain-of-function (GOF) mutations of the sodium-activated potassium channel KNa1.1 (Slack, Slo2.2, or KCa4.1) induce severe, drug-resistant forms of epilepsy in infants and children. Although quinidine has shown promise in treating KCNT1-related epilepsies compared to other drugs, its limited efficacy and substantial side effects necessitate the development of new KNa1.1 channel inhibitors. In this study, we developed a novel class of KNa1.1 inhibitors using combined silico approaches and structural optimization. Among these inhibitors, compound Z05 was identified as a selective potential KNa1.1 inhibitor, especially against the hERG channel. Moreover, its binding site and potential counteraction to a GOF mutant Y796H were identified by the mutation studies. Our data also showed that Z05 had significant pharmacological profiles, including high brain penetration and moderate oral bioavailability, offering a valuable in vitro tool compound for further drug development in treating KCNT1-related epilepsies.

A Rapid Analysis Method for Determination of Hydrocarbon Types in Aviation Turbine Fuel by Gas Chromatography-Mass Spectrometry.

A rapid analysis method for determination of hydrocarbon types in aviation turbine fuel was investigated in this study. A kind of reversible adsorption material packed as an unsaturated trap was used to separate saturated hydrocarbons and unsaturated hydrocarbons in the GC-MS system. No manual process or organic reagent was needed during the entire analysis process. The contents of 13 kinds of hydrocarbons, including paraffins, monocycloparaffins, dicycloparaffins, tricycloparaffins, monoolefins, cycloolefins, alkylbenzenes, CnH2n-8 aromatics, CnH2n-10 aromatics, naphthalenes, CnH2n-14 aromatics, CnH2n-16 aromatics, and CnH2n-18 aromatics were calculated by the characteristic mass fragments detected by MS with the modified matrices of ASTM D2425. The overall analysis time was less than 10 min. The precision of this test method has been conducted with 8 laboratories attended and 16 samples analyzed. The performance of this new method was demonstrated by comparing the results tested by ASTM D1319, ASTM D2425, and ASTM D6379. This rapid analysis method can provide hydrocarbon compositions of aviation turbine fuels or other liquid hydrocarbon samples within the same distillation range.

Molecular Engineering Chemical Pre-lithiation Reagent with Low Redox Potential for Graphite Anode Enables High Coulombic Efficiency.

Graphite (Gr) is a low-cost and high-stability anode for lithium-ion batteries (LIBs). However, Gr anode exhibits an obstinate drawback of low initial Coulombic efficiency (ICE), owing to the active lithium loss for the solid electrolyte interphase (SEI) layer. Herein, a straightforward and effective chemical pre-lithiation strategy is proposed to compensate for the lithium loss. A molecular engineering phenanthrene-based lithium-arene complex (Ph-based LAC) reagent is designed by density functional theory (DFT) calculations. The engineering Ph-based reagent enhances the stability of the π-electron system and the electron-donating capacity, resulting in a reduced redox potential to facilitate lithium transfer. The electrochemical distinct of the Ph-based reagent is illustrated, the prelithiation process in a low Li-insertion platform, and the lithiation degree is controllable with the dipping time (ICE = 102%, 3min). Notably, a denser and homogeneous SEI layer has pre-formed to enhance the Li+ transport and interface stability. Moreover, the lithium-ion full batteries assemble with LiFePO4 and NCM811 cathode, which exhibits high ICE (96.5% and 90.3%) and energy density (310 and 333Whkg-1). These findings present a facile and controllable pre-lithiation strategy to compensate for the lithium of LIBs, providing new valuable insights into the design and optimization of battery manufacture.

Catalytic Strategies for the Selective Synthesis of α‐ and β‐Functionalized Amines via Hydrofunctionalization of Enamides

α‐ and β‐functionalized amines are two classes of important compounds, whose structural units are widely present in approved drugs. The hydrofunctionalization of enamides is the most direct and efficient method for constructing these two types of compounds. The regioselectivity was the focus of this conversion, which is largely influenced by the catalytic mode. Therefore, in order to selectively synthesize α‐ or β‐functionalized amines, the progress in catalytic hydrofunctionalization of enamides over the past decade are reviewed, and the catalytic pathways for the hydrofunctionalization of enamides are discussed in detail. This account aims to objectively evaluate the effects of various catalytic pathways on the regioselectivity of hydrofunctionalization, in order to provide a new perspective on the selection of catalytic methods and the design of catalytic pathways for selective synthesis α‐ or β‐functionalized amines. This review has been divided into the following sections: 1. Introduction 2. Organic reagents catalysis 3. Transition metal catalysis 4. Photoredox catalysis 5. Summary and prospect Keywords: α‐ and β‐functionalized amines; enamides; regioselectivity; hydrofunctionalization; catalytic strategies

Evaluation of STK17B as a cancer immunotherapy target utilizing highly potent and selective small molecule inhibitors.

The serine/threonine kinase 17B (STK17B) is involved in setting the threshold for T cell activation and its absence sensitizes T cells to suboptimal stimuli. Consequently, STK17B represents an attractive potential target for cancer immunotherapy. To assess the potential of STK17B as an immuno-oncology target, we developed potent and selective tool compounds from starting points in Blueprint Medicines Corporation's proprietary kinase inhibitor library. To characterize these molecules, enzyme and cellular assays for STK17A and STK17B were established to drive chemistry optimization. Mass spectrometry-based phosphoproteomics profiling with tool inhibitors led to the identification of Ser19 on myosin light chain 2 as STK17B substrate, which is then developed into a flow cytometry-based pharmacodynamic readout of STK17B inhibition both in vitro and in vivo. In a mouse T cell activation assay, STK17B inhibitors demonstrated the ability to enhance interleukin-2 (IL-2) production. Similarly, treatment with STK17B inhibitors resulted in stronger cytokine secretion in human T cells activated using a T cell bispecific antibody. Subsequent chemistry optimization led to the identification of a highly selective and orally bioavailable tool compound, BLU7482. In vivo, STK17B inhibition led to dose-dependent modulation of myosin light chain 2 phosphorylation and enhanced priming of naïve T cells, as determined by upregulation of CD69, IL-2 and interferon-γ secretion. In line with increased T cell activation, treatment with STK17B inhibitor enhanced antitumor activity of anti-PD-L1 antibody in the MCA205 model. In summary, we successfully identified and optimized STK17B kinase inhibitors which led to increased T cell responses in vitro and in vivo. This allowed us to evaluate the potential of STK17B inhibition as an approach for cancer immunotherapy.

IL-6 and INF-γ Mediated Immune Responses in Mice Induced by Campylobacter jejuni Bacterial Ghosts

Background: Bacterial ghosts (BGs) a growing interest in their potential medical and pharmacological uses in recent years which is just. The empty bacterial envelopes Absent its internal substance .in this study using BGs for campylobacter jejuni which is curved, non- spore -forming, gram -negative rods that measure approximately 0.2 to 0.9µ₥×0.5 to 5.0 µ₥. Enteric campylobacter may appear as long spirals or S-or seagull -wing shapes. these organisms may appear as coccobacilli in smears prepared older cultures. Methods: On gram stained smears, these organisms stain poorly for better visualization carbol- fuchsin is recommended as a counterstain, if safranin is used, counterstaining should be extended to 2 to 3 minutes campylobacter spp. is motil. There are two methods for preparation of (BGs) either by E-lysis gene creating a lysis tunnel structure inside the active bacteria's envelope. Or by using minimum inhibition concentration and minimum growth concentration for chemical compounds (MIC), (MGC) in a row. The ideal circumstances for the generation of BGs were mapped using the Plackett-Burman experimental design using two experimental. Results: A spectrophotometer was used to measure the amount of DNA and protein released. The whole experiment was divided into three steps: in the first step all the chemical reagents except H2O2 were added to bacterial suspension, in the second step only H2O2, and in the third step, the cell pellets reconstituted in 60% ethanol and kept at room temperature for thirty minutes with gentle swirl of the cells for thirty seconds every five minutes. Cell pellets were gathered and cleaned again using the same procedure as mentioned. It was assured that no living cells were left behind in the bacterial spoon by cultivation using N.B. after the experiment. The lab animal Mic injected with BG from Campylobacter jejuni as a vaccine 28 days from the last immunization, which used the qPCR technique for the immune test, has been chosen. IL-6 and INF-G for this test. Conclusion: The immune responses accorded as a result of giving the vaccine was obtained from this the results of this research.

Blocking endogenous phosphorus release in sediments by a hydrotalcite mixture synthesized with natural sepiolite and discarded cans

Pure hydrotalcite (LDH) materials prepared from chemical reagents have been investigated as solid-phase phosphorus (P) inactivation materials (SPIM) to manage endogenous P loading in sediments. However, the efficacy and mechanism of LDH mixtures prepared by natural minerals and solid wastes in controlling sediment P release are unclear. Therefore, a Ca/Mg-Al-LDH (CMA-LDH) material was synthesized using sepiolite and cans, and its efficacy, mechanism, and ecological impact in controlling sediment P release were investigated. CMA-LDH-p was prepared as a control material using pure chemical reagents. The CMA-LDH and CMA-LDH-p were both composed of hydrotalcite and hydrocalumite. The maximum P adsorption capacity of CMA-LDH was 123.01 mg/g, comparable to that of CMA-LDH-p. The adsorbed P by CMA-LDH was mostly in the stable P form, accounting for 87.2 % of the total P. The adsorption capacity and immobilization ability of CMA-LDH for P were superior to other reported LDH-based SPIM. Both the CMA-LDH addition and capping successfully blocked sediment P release under anaerobic conditions. Passivation of mobile P in the sediment and DGT-labile P in the interstitial water was critical to preventing sediment P release by the CMA-LDH addition. The CMA-LDH capping inhibited sediment P release through the effective adsorption of CMA-LDH on DGT-labile P at the sediment/overlying water interface. The CMA-LDH addition and capping affected the abundance of microbial communities associated with iron and sulfur cycling, which might affect the stability of endogenous P. These results confirmed that CMA-LDH addition and capping treatments were effective methods for managing sediment P loading.

Treatment and Recycling of Tungsten Beneficiation Wastewater: A Review

The large amount of wastewater containing various pollutants generated during the tungsten beneficiation process has become a bottleneck for the sustainable development of tungsten mining enterprises. Typical pollutants mainly include suspended solids (SSs), silicate ions, metal ions, and residual organic reagents. The direct discharge of untreated tungsten beneficiation wastewater can cause serious harm to the ecological environment, while recycling can significantly affect flotation indicators. In this paper, the sources and characteristics of typical pollutants were analyzed, and various purification techniques were outlined, including coagulation, adsorption, chemical precipitation, oxidation, and biological treatment methods. Among these techniques, coagulation is particularly effective for the removal of SSs, while adsorption and chemical precipitation are recommended for the removal of soluble ions. For residual organic reagents, oxidation methods have demonstrated high treatment efficiencies. The mainstream methods for wastewater recycling were summarized, including centralized recycling, as well as internal recycling at certain stages. For tungsten beneficiation such a complex process, where the quality of wastewater varies greatly between different stages, it is suitable to recycle the wastewater after appropriate treatment at a specific stage. Furthermore, this study provided a perspective on the future directions of tungsten beneficiation wastewater treatment, serving as a reference for related research and industrial practices.

CaCO3-activited N-doped diatom biochar for the degradation of tetracycline

In this study, a N-doped diatom biochar (DBC) was prepared by one-step pyrolysis, where CaCO3 formed by marine diatom-mediated calcification was employed as an activator. Due to the activation effect of CaCO3, the specific surface area of the obtained DBC increased by more than 10 times, and the nitrogen presented as pyrrolic nitrogen (58.9%), pyridinic nitrogen (29.7%), and graphitic nitrogen (11.4%) in the DBC. In addition, the effects of important parameters and co-existing ions on the catalytic decomposition of tetracycline (TC) by DBC were investigated by using TC as a typical pollutant and PDS as an oxidant. The DBC/PDS system exhibited high activity over a broad pH range. Through radical scavenging experiments, electron spin resonance, and electrochemical results analysis, it was found that the degradation of TC in the system included both radical and nonradical pathways, and the most dominant reactive species was 1O2. Furthermore, the surficial reactive complexes formed by PDS on the catalysts also played an important role in attacking the adsorbed TC molecules. This study proposes an eco-friendly and economical technique to construct a clean advanced oxidation process capable of treating TC wastewater by utilizing the native biomass of diatom as a metal-free and efficient biochar catalyst while simultaneously reducing the use of chemical reagents.

A cross-disease resource of living human microglia identifies disease-enriched subsets and tool compounds recapitulating microglial states.

Human microglia play a pivotal role in neurological diseases, but we still have an incomplete understanding of microglial heterogeneity, which limits the development of targeted therapies directly modulating their state or function. Here, we use single-cell RNA sequencing to profile 215,680 live human microglia from 74 donors across diverse neurological diseases and CNS regions. We observe a central divide between oxidative and heterocyclic metabolism and identify microglial subsets associated with antigen presentation, motility and proliferation. Specific subsets are enriched in susceptibility genes for neurodegenerative diseases or the disease-associated microglial signature. We validate subtypes in situ with an RNAscope-immunofluorescence pipeline and high-dimensional MERFISH. We also leverage our dataset as a classification resource, finding that induced pluripotent stem cell model systems capture substantial in vivo heterogeneity. Finally, we identify and validate compounds that recapitulate certain subtypes in vitro, including camptothecin, which downregulates the signature of disease-enriched subtypes and upregulates a signature previously associated with Alzheimer's disease.