Metalloradical Catalysis: General Approach for Controlling Reactivity and Selectivity of Homolytic Radical Reactions.

Since Friedrich Wöhler's groundbreaking synthesis of urea in 1828, organic synthesis over the past two centuries has predominantly relied on the exploration and utilization of chemical reactions rooted in two-electron heterolytic ionic chemistry. While one-electron homolytic radical chemistry is both rich in fundamental reactivities and attractive with practical advantages, the synthetic application of radical reactions has been long hampered by the formidable challenges associated with the control over reactivity and selectivity of high-energy radical intermediates. To fully harness the untapped potential of radical chemistry for organic synthesis, there is a pressing need to formulate radically different concepts and broadly applicable strategies to address these outstanding issues. In pursuit of this objective, researchers have been actively developing metalloradical catalysis (MRC) as a comprehensive framework to guide the design of general approaches for controlling over reactivity and stereoselectivity of homolytic radical reactions. Essentially, MRC exploits the metal-centered radicals present in open-shell metal complexes as one-electron catalysts for homolytic activation of substrates to generate metal-entangled organic radicals as the key intermediates to govern the reaction pathway and stereochemical course of subsequent catalytic radical processes. Different from the conventional two-electron catalysis by transition metal complexes, MRC operates through one-electron chemistry utilizing stepwise radical mechanisms.

Wildfire exposure and academic performance in Brazil: A causal inference approach for spatiotemporal data.

As the frequency and intensity of wildfires are projected to globally amplify due to climate change, there is a growing need to quantify the impact of exposure to wildfires in vulnerable populations such as adolescents. In our study, we applied rigorous causal inference methods to estimate the effect of wildfire exposure on the academic performance of high school students in Brazil between 2009 and 2015. Using longitudinal data from 8,183 high schools across 1,571 municipalities in Brazil, we estimated that the average performance in most academic subjects decreases under interventions that increase wildfire exposure, e.g., a decrease of 1.8 % (p = 0.01) in the natural sciences when increasing the wildfire density from 0.0035 wildfires/km2 (first quantile in the sample) to 0.0222 wildfires/km2 (third quartile). Furthermore, these effects considerably worsened over time. Our findings highlight the adverse impact of wildfires on educational outcomes.

Iron(III)-based metalloradical catalysis for asymmetric cyclopropanation via a stepwise radical mechanism.

Metalloradical catalysis (MRC) exploits the metal-centred radicals present in open-shell metal complexes as one-electron catalysts for the generation of metal-stabilized organic radicals-key intermediates that control subsequent one-electron homolytic reactions. Cobalt(II) complexes of porphyrins, as stable 15e-metalloradicals with a well-defined low-spin d7 configuration, have dominated the ongoing development of MRC. Here, to broaden MRC beyond the use of Co(II)-based metalloradical catalysts, we describe systematic studies that establish the operation of Fe(III)-based MRC and demonstrate an initial application for asymmetric radical transformations. Specifically, we report that five-coordinate iron(III) complexes of porphyrins with an axial ligand, which represent another family of stable 15e-metalloradicals with a d5 configuration, are potent metalloradical catalysts for olefin cyclopropanation with different classes of diazo compounds via a stepwise radical mechanism. This work lays a foundation and mechanistic blueprint for future exploration of Fe(III)-based MRC towards the discovery of diverse stereoselective radical reactions.

Quantifying the potential effects of air pollution reduction on population health and health expenditure in Taiwan.

Air pollution, particularly ambient fine particulate matter (PM2.5) pollution, poses a significant risk to public health, underscoring the importance of comprehending the long-term impact on health burden and expenditure at national and subnational levels. Therefore, this study aims to quantify the disease burden and healthcare expenditure associated with PM2.5 exposure in Taiwan and assess the potential benefits of reducing pollution levels. Using a comparative risk assessment framework that integrates an auto-aggressive integrated moving average model, we evaluated the avoidable burden of cardiopulmonary diseases (including ischemic heart disease, stroke, chronic obstructive pulmonary disease, lung cancer, and diabetes mellitus) and related healthcare expenditure under different air quality target scenarios, including status quo and target scenarios of 15, 10, and 5 µg/m3 reduction in PM2.5 concentration. Our findings indicate that reducing PM2.5 exposure has the potential to significantly alleviate the burden of multiple diseases. Comparing the estimated attributable disease burden and healthcare expenditure between reference and target scenarios from 2022 to 2050, the avoidable disability-adjusted life years were 0.61, 1.83, and 3.19 million for the 15, 10, and 5 µg/m3 target scenarios, respectively. Correspondingly, avoidable healthcare expenditure ranged from US$ 0.63 to 3.67 billion. We also highlighted the unequal allocation of resources and the need for policy interventions to address health disparities due to air pollution. Notably, in the 5 µg/m3 target scenario, Kaohsiung City stands to benefit the most, with 527,368 disability-adjusted life years avoided and US$ 0.53 billion saved from 2022 to 2050. Our findings suggest that adopting stricter emission targets can effectively reduce the health burden and associated healthcare expenditure in Taiwan. Overall, this study provides policymakers in Taiwan with valuable insights for mitigating the negative effects of air pollution by establishing a comprehensive framework for evaluating the co-benefits of air pollution reduction on healthcare expenditure and disease burden.

Asymmetric Radical Bicyclization for Stereoselective Construction of Tricyclic Chromanones and Chromanes with Fused Cyclopropanes.

Asymmetric radical bicyclization processes have been developed via metalloradical catalysis (MRC) to stereoselectively construct chiral chromanones and chromanes bearing fused cyclopropanes. Through optimization of a versatile D2-symmetric chiral amidoporphyrin ligand platform, a Co(II)-metalloradical system can homolytically activate both diazomalonates and α-aryldiazomethanes containing different alkene functionalities under mild conditions for effective radical bicyclization, delivering cyclopropane-fused tricyclic chromanones and chromanes, respectively, in high yields with excellent control of both diastereoselectivities and enantioselectivities. Combined computational and experimental studies, including the electron paramagnetic resonance (EPR) detection and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) trapping of key radical intermediates, shed light on the working details of the underlying stepwise radical mechanisms of the Co(II)-catalyzed bicyclization processes. The two catalytic radical processes provide effective synthetic tools for stereoselective construction of valuable cyclopropane-fused chromanones and chromanes with newly generated contiguous stereogenic centers. As a specific demonstration of synthetic application, the Co(II)-catalyzed radical bicyclization has been employed as a key step for the first asymmetric total synthesis of the natural product (+)-Radulanin J.

Healthcare utilization and comorbidity shortly before suicide mortality in patients with attention-deficit/hyperactivity disorder: a nested case-control study.

BACKGROUND: Few studies have analyzed healthcare utilization before suicide among individuals with attention-deficit/hyperactivity disorder (ADHD). This study examined the pattern of healthcare utilization and comorbidities shortly before death among patients with ADHD who died by suicide and compared these data with those of living controls. This study used Taiwan's National Health Insurance Research Database to identify patients with ADHD (N = 379,440) between January 1, 2001, and December 31, 2016. Subsequently, the researchers identified 159 suicide decedents by linking each patient with the National Mortality Database. By conducting a nested case-control study with risk-set sampling from the ADHD cohort, the researchers selected 20 age- and sex-matched controls (n = 3180) for each patient who died by suicide (cases). The researchers then applied conditional logistic regression to investigate differences in healthcare utilization as well as psychiatric and physical comorbidities between case patients and controls. Case patients had higher healthcare utilization within 3 months before suicide, particularly in the psychiatry, emergency, internal medicine, neurosurgery, and plastic surgery departments. These patients also had higher risks of psychiatric comorbidities, including schizophrenia, bipolar disorder, depressive disorder, and sleep disorder, as well as physical comorbidities such as hypertension and other forms of heart disease. Among patients with ADHD, suicide decedents had increased healthcare utilization and higher risks of specific psychiatric and physical comorbidities than living controls. Thus, for suicide prevention among individuals with ADHD, suicide risk must be detected early and comorbidities should be adequately managed.

Healthcare utilization, psychiatric disorders, and physical illnesses shortly before suicide mortality in adolescents in Taiwan.

BACKGROUND: This study examined the pattern of medical utilization and the distribution of comorbidities shortly before death among adolescents who died from suicide and compared these data with those of living controls. METHODS: From Taiwan's National Health Insurance Research Database, this study identified adolescents aged 10-19 years who died from suicide (n = 935) between 1 January 2000, and 31 December 2016, by linking each patient with the national mortality database. The researchers conducted a nested case-control study through risk set sampling, and for each case, 20 age- and sex-matched controls (n = 18 700) were selected from the general population. The researchers applied conditional logistic regression to investigate differences in medical utilization and physical and psychiatric comorbidities between cases and controls. RESULTS: Cases had a higher proportion of contact with the psychiatric department but a similar proportion of contact with any non-psychiatric medical department within 1 year before suicide compared with controls. There were 18.6% of adolescent suicide victims who only had contacted with a psychiatric department 3 months before suicide. Moreover, cases had a higher proportion of contact with non-psychiatric services within 3 months before suicide, particularly with emergency, surgery, and internal medicine departments. Cases had higher risks of several psychiatric disorders and physical illnesses, including heart diseases, pneumonia, and ulcer disease, than did controls. CONCLUSIONS: The findings of increased medical utilization and higher risks of physical and psychiatric comorbidities in adolescent suicide victims are crucial for developing specific interventions to prevent suicide in this population.

Acculturation, Work-Related Stressors, and Respective Coping Strategies among Male Indonesian Migrant Workers in the Manufacturing Industry in Taiwan: A Post-COVID Investigation.

Globalization has prompted cross-cultural migration in search of employment opportunities, and poor adaptation during acculturation is widely known to cause additional psychosocial stress. Hence, the objective of this study was to investigate migrant workers' perceptions of acculturation, identify work-related stressors, and understand the respective coping strategies among male Indonesians in the manufacturing industry, particularly during the COVID-19 pandemic. Fifteen workers were recruited and interviewed on their acculturation experiences. We found that the workers were susceptible to forced adaptation to stressful conditions relating to work organization, economic distress, interaction with the manpower agencies, language barriers, and so on. During the pandemic, workers experienced overload, economic hardship, suspended home visits, isolation, discrimination, and fear of cluster infection in the crowded dormitory. We also found that workers were able to adopt coping strategies by capitalizing on resources at the individual, institutional, and governmental policy levels to actively solve problems, increase emotional support, and fortify self-appraisals. The identified coping strategies could inform policy development to assist with positive adaptation and promote the well-being of the migrant worker population.

Radical differentiation of two ester groups in unsymmetrical diazomalonates for highly asymmetric olefin cyclopropanation.

Diazomalonates have been demonstrated as effective metalloradicophiles for asymmetric radical olefin cyclopropanation via Co(II)-metalloradical catalysis (MRC). Supported by D 2-symmetric chiral amidoporphyrin ligand, Co(II)-based metalloradical system can efficiently activate unsymmetrical methyl phenyl diazomalonate (MPDM) with effective differentiation of the two ester groups for asymmetric cyclopropanation, enabling stereoselective construction of 1,1-cyclopropanediesters bearing two contiguous chiral centers, including all-carbon quaternary stereogenic center. The Co(II)-catalyzed asymmetric cyclopropanation, which operates at room temperature without slow addition of the diazo compound, is generally applicable to broad-ranging olefins and tolerates various functionalities, providing a streamlined synthesis of chiral 1,1-cyclopropanediesters in high yields with both high diastereoselectivity and enantioselectivity. Combined computational and experimental studies support the underlying stepwise radical mechanism for Co(II)-catalyzed cyclopropanation. In addition to functioning as 1,3-dipoles for forming five-membered structures, enantioenriched (E)-1,1-cyclopropanediesters serve as useful building blocks for stereoselective synthesis of different cyclopropane derivatives. In addition, the enantioenriched (E)-1,1-cyclopropanediesters can be stereoselectively converted to (Z)-diastereomers.

Metalloradical Activation of In Situ-Generated α-Alkynyldiazomethanes for Asymmetric Radical Cyclopropanation of Alkenes.

α-Alkynyldiazomethanes, generated in situ from the corresponding sulfonyl hydrazones in the presence of a base, can serve as effective metalloradicophiles in Co(II)-based metalloradical catalysis (MRC) for asymmetric cyclopropanation of alkenes. With D2-symmetric chiral amidoporphyrin 2,6-DiMeO-QingPhyrin as the optimal supporting ligand, the Co(II)-based metalloradical system can efficiently activate different α-alkynyldiazomethanes at room temperature for highly asymmetric cyclopropanation of a broad range of alkenes. This catalytic radical process provides a general synthetic tool for stereoselective construction of alkynyl cyclopropanes in high yields with high both diastereoselectivity and enantioselectivity. Combined computational and experimental studies offer several lines of evidence in support of the underlying stepwise radical mechanism for the Co(II)-catalyzed olefin cyclopropanation involving a unique α-metalloradical intermediate that is associated with two resonance forms of α-Co(III)-propargyl radical and γ-Co(III)-allenyl radical. The resulting enantioenriched alkynyl cyclopropanes, as showcased with several stereospecific transformations, may serve as valuable chiral building blocks for stereoselective organic synthesis.

Increased medical utilization and psychiatric comorbidity following a new diagnosis of methamphetamine use disorder.

Background: Evidence of patterns of medical utilization and distribution of comorbidities among individuals using methamphetamine remains limitedObjective: This study aims to investigate changes in medical utilization and comorbidities before and after a diagnosis of methamphetamine use disorder.Methods: A total of 3321 cases (79% were male) of methamphetamine use disorder between January 1, 1996, and December 31, 2012, were identified from Psychiatric Inpatient Medical Claims database in Taiwan. Information was collected on demographics, diagnoses, and medical utilizations. The date of newly diagnosed with methamphetamine use disorder was defined as the baseline. Mirror-image study design was used to compare changes in medical utilization and comorbidities between the pre-baseline period (within 1 year before diagnosis) and the post-baseline period (within 1 year after diagnosis). Conditional logistic regression was used to estimate changes in medical utilization and comorbidities.Results: Most cases (77%) were first identified in a psychiatric department. There is a significant increase (P < .001) in psychiatric admission (odds ratio[OR] = 2.19), psychiatric emergency visits (OR = 1.31), and psychiatric outpatient visits (OR = 1.15) after diagnosis. Multivariable analysis revealed significantly increased risks (P < .001) of non-methamphetamine drug induced mental disorders (adjusted OR[aOR] = 29.47), schizophrenia (aOR = 2.62), bipolar disorder (aOR = 2.14), organic mental disorder (aOR = 1.82), and upper respiratory tract infection (aOR = 2.03) after diagnosis.Conclusions: We found significant increases of medical utilization and psychiatric comorbidities after diagnosed with methamphetamine use disorder. These findings may reflect the problem of delayed diagnosis and treatment. Enhancement of early identification of methamphetamine use disorder in general practice is required for early intervention and decreased subsequent morbidities.

Healthcare utilization and psychiatric and physical comorbidities before suicide mortality in patients with methamphetamine use disorder: A nationwide case-control study.

BACKGROUND: Since the late 1990s, methamphetamine use has become a considerable public health concern. Despite high suicide rates among methamphetamine users, studies exploring medical utilization and psychiatric and physical comorbidities before suicide are scant. We aim to examine the pattern of medical utilization and distribution of comorbidities shortly before suicide in methamphetamine users who died of suicide and compared these data with those of living methamphetamine users. METHODS: From Taiwan's National Health Insurance Research Database, we identified the cohort with methamphetamine use disorder (n = 23,248) between January 1, 2001, and December 31, 2005. We identified 5972 deceased patients (of whom 745 died of suicide) by linking each patient with the national mortality database during the study period. By conducting a nested case-control study with risk-set sampling, from the methamphetamine cohort, we selected four age- and sex-matched controls for each patient who died of suicide (cases). We applied conditional logistic regression to investigate differences in medical utilization and physical and psychiatric comorbidities between cases and controls. RESULTS: Cases had higher medical utilization within 3 months before suicide, particularly in the departments of psychiatry, internal medicine, emergency, and family practice. Cases had higher risks of physical comorbidities, including pneumonia and renal disease, and psychiatric comorbidities, including depressive disorder, sleep disorder, drug-induced mental disorder, schizophrenia, and bipolar disorder. CONCLUSIONS: The findings of increased medical utilization and the higher risks of physical and psychiatric comorbidities in cases are crucial for developing specific interventions to prevent suicide in this patient population.

Combined radical and ionic approach for the enantioselective synthesis of ß-functionalized amines from alcohols.

Chiral amines are among the most important organic compounds and have widespread applications. Enantioselective construction of chiral amines is a major aim in organic synthesis. Among synthetic methods, direct functionalization of omnipresent C-H bonds with common organic nitrogen compounds represents one of the most attractive strategies. However, C-H amination strategies are largely limited to constructing a specific type of N-heterocycles or amine derivatives. To maximize the synthetic potential of asymmetric C-H amination, we report here an approach that unites the complementary reactivities of radical and ionic chemistry for streamlined synthesis of functionalized chiral amines. This synthesis merges the development of an enantioselective radical process for 1,5-C(sp 3)-H amination of alkoxysulfonyl azides via Co(II)-based metalloradical catalysis with an enantiospecific ionic process for ring-opening of the resulting five-membered chiral sulfamidates by nucleophiles. Given that alkoxysulfonyl azides are derived from the corresponding alcohols, this approach offers a powerful synthetic tool for enantioselective ß-C-H amination of common alcohols while converting the hydroxy group to other functionalities through formal nucleophilic substitution.

Asymmetric Radical Cyclopropanation of Dehydroaminocarboxylates: Stereoselective Synthesis of Cyclopropyl α-Amino Acids.

A catalytic radical process has been developed for asymmetric cyclopropanation of dehydroaminocarboxylates with in situ-generated α-aryldiazomethanes via Co(II)-based metalloradical catalysis (MRC). Through fine-tuning the environments of D 2-symmetric chiral amidoporphyrin platform as the supporting ligands, the Co(II)-metalloradical system can effectively activate various α-aryldiazomethanes to cyclopropanate different dehydroaminocarboxylates under mild conditions, enabling the stereoselective synthesis of chiral cyclopropyl α-amino acid derivatives. In addition to high yields and excellent enantioselectivities, the Co(II)-catalyzed asymmetric radical cyclopropanation exhibits (Z)-diastereoselectivity, which is the opposite of uncatalyzed thermal reaction. Combined computational and experimental studies support a stepwise radical mechanism for the Co(II)-catalyzed cyclopropanation reaction. The resulting enantioenriched (Z)-α-amino-ß-arylcyclopropanecarboxylates, as showcased for the efficient synthesis of dipeptides, may serve as unique non-proteinogenic amino acid building blocks for the design and preparation of novel peptides with restricted conformations.

Exploring the mediating role of methamphetamine use in the relationship between adverse childhood experiences and attempted suicide.

OBJECTIVE: Methamphetamine (METH) use and adverse childhood experiences (ACEs) has been associated with an increased risk of suicidal behaviour. However, whether METH use underlies the risk of suicide attributable to ACEs is unknown and warrants investigation to inform preventive interventions. In this study, we examined the mediating role of METH use in the relationship between attempted suicide and ACEs. METHOD: METH users recruited from a mandatory detoxification center (n = 346) and healthy controls (n = 342) both completed a survey related to 9 types of ACE, which was based the Family Health Questionnaire. A lifetime history of attempted suicide was obtained using the Chinese version of the Composite International Diagnostic Interview. We conducted a bootstrapped mediation analysis to examine the mediating effect of METH use on the association between ACEs and attempted suicide. RESULTS: Female gender, METH use, and having multiple (≥3) ACEs were associated with an increased risk of attempted suicide. A dose-response relationship between the number of ACEs and suicide rate was observed among individuals with METH use. METH use significantly mediated the association between ACEs and attempted suicide in those with multiple (2 and 3 ACEs respectively with proportion mediated 0.16 and 0.42) and specific types of ACEs (physical abuse, witnessing maternal battering, household substance abuse, sexual abuse, and parental separation with proportion mediated 0.25, 0.35, 0.38, 0.48, 0.47 respectively). CONCLUSION: Our study is the first to demonstrate that METH use partially mediates the association between ACEs and attempted suicide. Addressing METH use in people with ACEs could reduce their suicide risk.

New Catalytic Radical Process Involving 1,4-Hydrogen Atom Abstraction: Asymmetric Construction of Cyclobutanones.

While alkyl radicals have been well demonstrated to undergo both 1,5- and 1,6-hydrogen atom abstraction (HAA) reactions, 1,4-HAA is typically a challenging process both entropically and enthalpically. Consequently, chemical transformations based on 1,4-HAA have been scarcely developed. Guided by the general mechanistic principles of metalloradical catalysis (MRC), 1,4-HAA has been successfully incorporated as a key step, followed by 4-exo-tet radical substitution (RS), for the development of a new catalytic radical process that enables asymmetric 1,4-C-H alkylation of diazoketones for stereoselective construction of cyclobutanone structures. The key to success is the optimization of the Co(II)-based metalloradical catalyst through judicious modulation of D2-symmetric chiral amidoporphyrin ligand to adopt proper steric, electronic, and chiral environments that can utilize a network of noncovalent attractive interactions for effective activation of the substrate and subsequent radical intermediates. Supported by an optimal chiral ligand, the Co(II)-based metalloradical system, which operates under mild conditions, is capable of 1,4-C-H alkylation of α-aryldiazoketones with varied electronic and steric properties to construct chiral α,ß-disubstituted cyclobutanones in good to high yields with high diastereoselectivities and enantioselectivities, generating dinitrogen as the only byproduct. Combined computational and experimental studies have shed light on the mechanistic details of the new catalytic radical process, including the revelation of facile 1,4-HAA and 4-exo-tet-RS steps. The resulting enantioenriched α,ß-disubstituted cyclobutanones, as showcased with several enantiospecific transformations to other types of cyclic structures, may find useful applications in stereoselective organic synthesis.

Controlling Enantioselectivity and Diastereoselectivity in Radical Cascade Cyclization for Construction of Bicyclic Structures.

Radical cascade cyclization reactions are highly attractive synthetic tools for the construction of polycyclic molecules in organic synthesis. While it has been successfully implemented in diastereoselective synthesis of natural products and other complex compounds, radical cascade cyclization faces a major challenge of controlling enantioselectivity. As the first application of metalloradical catalysis (MRC) for controlling enantioselectivity as well as diastereoselectivity in radical cascade cyclization, we herein report the development of a Co(II)-based catalytic system for asymmetric radical bicyclization of 1,6-enynes with diazo compounds. Through the fine-tuning of D2-symmetric chiral amidoporphyrins as the supporting ligands, the Co(II)-catalyzed radical cascade process, which proceeds in a single operation under mild conditions, enables asymmetric construction of multisubstituted cyclopropane-fused tetrahydrofurans bearing three contiguous stereogenic centers, including two all-carbon quaternary centers, in high yields with excellent stereoselectivities. Combined computational and experimental studies have shed light on the underlying stepwise radical mechanism for this new Co(II)-based cascade bicyclization that involves the relay of several Co-supported C-centered radical intermediates, including α-, ß-, γ-, and ε-metalloalkyl radicals. The resulting enantioenriched cyclopropane-fused tetrahydrofurans that contain a trisubstituted vinyl group at the bridgehead, as showcased in several stereospecific transformations, may serve as useful intermediates for stereoselective organic synthesis. The successful demonstration of this new asymmetric radical process via Co(II)-MRC points out a potentially general approach for controlling enantioselectivity as well as diastereoselectivity in synthetically attractive radical cascade reactions.

Estimating climate change-related impacts on outdoor air pollution infiltration.

BACKGROUND: Rising temperatures due to climate change are expected to impact human adaptive response, including changes to home cooling and ventilation patterns. These changes may affect air pollution exposures via alteration in residential air exchange rates, affecting indoor infiltration of outdoor particles. We conducted a field study examining associations between particle infiltration and temperature to inform future studies of air pollution health effects. METHODS: We measured indoor fine particulate matter (PM2.5) in Atlanta in 60 homes (810 sampling-days). Indoor-outdoor sulfur ratios were used to estimate particle infiltration, using central site outdoor sulfur concentrations. Linear and mixed-effects models were used to examine particle infiltration ratio-temperature relationships, based on which we incorporated projected meteorological values (Representative Concentration Pathways intermediate scenario RCP 4.5) to estimate particle infiltration ratios in 20-year future (2046-2065) and past (1981-2000) scenarios. RESULTS: The mean particle infiltration ratio in Atlanta was 0.70 ± 0.30, with a 0.21 lower ratio in summer compared to transition seasons (spring, fall). Particle infiltration ratios were 0.19 lower in houses using heating, ventilation, and air conditioning (HVAC) systems compared to those not using HVAC. We observed significant associations between particle infiltration ratios and both linear and quadratic models of ambient temperature for homes using natural ventilation and those using HVAC. Future temperature was projected to increase by 2.1 °C in Atlanta, which corresponds to an increase of 0.023 (3.9%) in particle infiltration ratios during cooler months and a decrease of 0.037 (6.2%) during warmer months. DISCUSSION: We estimated notable changes in particle infiltration ratio in Atlanta for different 20-year periods, with differential seasonal patterns. Moreover, when stratified by HVAC usage, increases in future ambient temperature due to climate change were projected to enhance seasonal differences in PM2.5 infiltration in Atlanta. These analyses can help minimize exposure misclassification in epidemiologic studies of PM2.5, and provide a better understanding of the potential influence of climate change on PM2.5 health effects.