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In the modern "omics" era, measurement of the human exposome is a critical missing link between genetic drivers and disease outcomes. High-resolution mass spectrometry (HRMS), routinely used in proteomics and metabolomics, has emerged as a leading technology to broadly profile chemical exposure agents and related biomolecules for accurate mass measurement, high sensitivity, rapid data acquisition, and increased resolution of chemical space. Non-targeted approaches are increasingly accessible, supporting a shift from conventional hypothesis-driven, quantitation-centric targeted analyses toward data-driven, hypothesis-generating chemical exposome-wide profiling. However, HRMS-based exposomics encounters unique challenges. New analytical and computational infrastructures are needed to expand the analysis coverage through streamlined, scalable, and harmonized workflows and data pipelines that permit longitudinal chemical exposome tracking, retrospective validation, and multi-omics integration for meaningful health-oriented inferences. In this article, we survey the literature on state-of-the-art HRMS-based technologies, review current analytical workflows and informatic pipelines, and provide an up-to-date reference on exposomic approaches for chemists, toxicologists, epidemiologists, care providers, and stakeholders in health sciences and medicine. We propose efforts to benchmark fit-for-purpose platforms for expanding coverage of chemical space, including gas/liquid chromatography-HRMS (GC-HRMS and LC-HRMS), and discuss opportunities, challenges, and strategies to advance the burgeoning field of the exposome.

Although progress has been made in enantioselective hydroboration of di- and trisubstituted alkenes over the past decades, enantioselective hydroboration of tetrasubstituted alkenes with high diastereo- and enantioselectivities continues as an unmet challenge since the 1950s due to its extremely low reactivity and the difficulties to simultaneously control the regio- and stereoselectivity of a tetrasubstituted alkene. Here, we report highly regio-, diastereo-, and enantioselective catalytic hydroboration of diverse acyclic tetrasubstituted alkenes. The delicate interplay of an electron-rich rhodium complex and coordination-assistance forms a highly adaptive catalyst that effectively overcomes the low reactivity and controls the stereoselectivity. The generality of the catalyst system is exemplified by its efficacy across various tetrasubstituted alkenes with diverse steric and electronic properties.

Catalytic branch-selective hydrofunctionalization of feedstock α-olefins to form enantioenriched chiral compounds is a particularly attractive yet challenging transformation in asymmetric catalysis. Herein we report an iridium-catalyzed asymmetric hydroalkenylation of α-olefins through directed C-H cleavage of enamides. This atom-economical addition process is highly branch-selective and enantioselective, delivering trisubstituted alkenes with an allylic stereocenter. DFT calculations reveal the origin of regio- and enantioselectivity.

Children in low- and middle-income countries are often exposed to higher levels of chemicals and are more vulnerable to the health effects of air pollution. Little is known about the diversity, toxicity, and dynamics of airborne chemical exposures at the molecular level. We developed a workflow employing state-of-the-art wearable passive sampling technology coupled with high-resolution mass spectrometry to comprehensively measure 147 children's personal exposures to airborne chemicals in Limpopo, South Africa, as part of the Venda Health Examination of Mothers, Babies, and Their Environment (VHEMBE). 637 environmental exposures were detected, many of which have never been measured in this population; of these 50 airborne chemical exposures of concern were detected, including pesticides, plasticizers, organophosphates, dyes, combustion products, and perfumes. Biocides detected in wristbands included p , p '-dichlorodiphenyltrichloroethane ( p , p '-DDT), p , p '-dichlorodiphenyldichloroethane ( p , p '-DDD), p , p '-dichlorodiphenyldichloroethylene ( p , p '-DDE), propoxur, piperonyl butoxide, and triclosan. Exposures differed across the assessment period with 27% of detected chemicals observed to be either higher or lower in the wet or dry seasons.

Exhaled respiratory droplets and aerosols can carry infectious viruses and are an important mode of transmission for COVID-19. Recent studies have been successful in detecting airborne SARS-CoV-2 RNA in indoor settings using active sampling methods. The cost, size, and maintenance of these samplers, however, limit their long-term monitoring ability in high-risk transmission areas. As an alternative, passive samplers can be small, lightweight, and inexpensive and do not require electrical power or maintenance for continual operation. Integration of passive samplers into wearable designs can be used to better understand personal exposure to the respiratory virus. This study evaluated the use of a polydimethylsiloxane (PDMS)-based passive sampler to assess personal exposure to aerosol and droplet SARS-CoV-2. The rate of uptake of virus-laden aerosol on PDMS was determined in lab-based rotating drum experiments to estimate time-weighted averaged airborne viral concentrations from passive sampler viral loading. The passive sampler was then embedded in a wearable clip design and distributed to community members across Connecticut to surveil personal SARS-CoV-2 exposure. The virus was detected on clips worn by five of the 62 participants (8%) with personal exposure ranging from 4 to 112 copies of SARS-CoV-2 RNA/m 3 , predominantly in indoor restaurant settings. Our findings demonstrate that PDMS-based passive samplers may serve as a useful exposure assessment tool for airborne viral exposure in real-world high-risk settings and provide avenues for early detection of potential cases and guidance on site-specific infection control protocols that preempt community transmission., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Chemical exposures are a major risk factor for many diseases. Comprehensive characterization of personal exposures is necessary to highlight chemicals of concern and factors that influence these chemical exposure dynamics. For this purpose, wearable passive samplers can be applied to assess longitudinal personal exposures to airborne contaminants. Questions remain regarding the impact of sampler placement at different locations of the body on the exposure profiles observed and how these placements affect the monitoring of seasonal dynamics in exposures. This study assessed personal air contaminant exposure using passive samplers worn in parallel across 32 participant's wrists, chest, and shoes over 24 h. Samplers were analyzed by thermal desorption gas chromatography high-resolution mass spectrometry. Personal exposure profiles were similar for about one-third of the 275 identified chemicals, irrespective of sampler placement. Signals of certain semivolatile organic compounds (SVOCs) were enhanced in shoes and, to a lesser extent, wrist samplers, as compared to those in chest samplers. Signals of volatile organic compounds were less impacted by sampler placement. Results showed that chest samplers predominantly captured more volatile exposures, as compared to those of particle-bound exposures, which may indicate predominant monitoring of chemicals via the inhalation route of exposure for chest samplers. In contrast, shoe samplers were more sensitive to particle-bound SVOCs. Seventy-one chemicals changed across participants between winter and summer in the same manner for two or more different sampler placements on the body, whereas 122 chemicals were observed to have seasonal differences in only one placement. Hence, the placement in certain cases significantly impacts exposure dynamics observed. This work shows that it is essential in epidemiological studies undertaking exposure assessment to consider the consequence of the placement of exposure monitors.