Synthesis of methanediol [CH2(OH)2]: The simplest geminal diol

Geminal diols—organic molecules carrying two hydroxyl groups at the same carbon atom—have been recognized as key reactive intermediates by the physical (organic) chemistry and atmospheric science communities as fundamental transients in the aerosol cycle and in the atmospheric ozonolysis reaction sequence. Anticipating short lifetimes and their tendency to fragment to water plus the aldehyde or ketone, free geminal diols represent one of the most elusive classes of organic reactive intermediates. Here, we afford an exceptional glance into the preparation of the previously elusive methanediol [CH₂(OH)₂] transient—the simplest geminal diol—via energetic processing of low-temperature methanol–oxygen ices. Methanediol was identified in the gas phase upon sublimation via isomer-selective photoionization reflectron time-of-flight mass spectrometry combined with isotopic substitution studies. Electronic structure calculations reveal that methanediol is formed via excited state dynamics through insertion of electronically excited atomic oxygen into a carbon–hydrogen bond of the methyl group of methanol followed by stabilization in the icy matrix. The first preparation and detection of methanediol demonstrates its gas-phase stability as supported by a significant barrier hindering unimolecular decomposition to formaldehyde and water. These findings advance our perception of the fundamental chemistry and chemical bonding of geminal diols and signify their role as an efficient sink of aldehydes and ketones in atmospheric environments eventually coupling the atmospheric chemistry of geminal diols and Criegee intermediates.

Since the turn of the century, geminal diols—defined as organic molecules carrying two hydroxyl groups (OH) at the same carbon atom—have been recognized as key reactive intermediates by the physical (organic) chemistry and atmospheric science communities as fundamental transients in the aerosol cycle (1–3). However, even the simplest representative of a geminal diol—methanediol [CH₂(OH)₂] (1′, 1″)—has not been isolated yet and is conjectured only to exist as short-lived intermediates in the troposphere and in aqueous solutions of formaldehyde (H₂CO) as a transient driven by the inherent dehydration tendency and instability of the two adjacent hydroxyl groups at the same carbon atom (4–7). This classifies geminal diols as one of the least-explored classes of organic reactive intermediates.Gas-phase electronic structure calculations predict that two conformers of methanediol [CH₂(OH)₂] (1′, 1″) are thermodynamically favorable compared to the well-known methyl peroxide isomer (CH₃OOH, 2) by 267 kJ ⋅ mol⁻¹ and 257 kJ ⋅ mol⁻¹, respectively; these conformers are also thermodynamically and kinetically stable toward unimolecular decomposition via dehydration to the formaldehyde–water complex (3), as the 1′ to 3 and 1″ to 3 reactions are endoergic by 21 and 11 kJ ⋅ mol⁻¹ and have barriers of 181 and 191 kJ ⋅ mol⁻¹, respectively (8–11) (Fig. 1). A second decomposition mechanism of 1′/1″ to formic acid (HCOOH) and molecular hydrogen (H₂) involves a transition state predicted to be even 159 kJ ⋅ mol⁻¹ higher than the barrier of the dehydration mechanism (12). Consequently, methanediol [CH₂(OH)₂] (1′, 1″) is expected to be thermodynamically and kinetically stable and hence should be detectable in the gas phase once prepared. However, envisaging the complexities of a directed gas-phase synthesis and short lifetimes of these reactive intermediates, free geminal diols signify one of the most elusive groups of organic transient molecules. This system is also attractive from the viewpoint of electronic structure theory and chemical bonding to benchmark the chemical reactivity and fundamental bond-breaking processes leading to geminal diols in extreme environments.Open in a separate windowFig. 1.Molecular structures of CH₄O₂ isomers. Relative energies, point groups, electronic ground states, and adiabatic ionization energies (blue) of CH₄O₂ isomers are also compiled. The energies were computed at the coupled cluster singles, doubles, and perturbative triples level with a complete basis set extrapolation [CCSD(T)/CBS] and include zero-point vibrational energy corrections. The atoms are color coded in gray (carbon), white (hydrogen), and red (oxygen). The formation of methanediol [(CH₂(OH)₂], 1’ and 1’’) and methyl peroxide (CH₃OOH, 2) via excited-state oxygen atom [O(¹D)] insertion into a carbon–hydrogen and carbon–oxygen/oxygen–hydrogen bonds of methanol (CH₃OH), respectively, are barrierless. The transition state of the decomposition of methanediol [(CH₂(OH)₂], 1’ and 1’’) to a formaldehyde (H₂CO) and water (H₂O) complex (H₂CO···H₂O, 3) is also shown.Here, we report the very first preparation of the previously elusive methanediol [CH₂(OH)₂] molecule (1’), along with its isomer methyl peroxide isomer (CH₃OOH) (2), through exposure of low-temperature (5 K) methanol (CH₃OH)–oxygen (O₂) ices to energetic electrons (SI Appendix, Tables S1–S4). The isomers were unambiguously identified in the gas phase upon sublimation in the temperature-programmed desorption (TPD) phase and discriminated through isomer-selective photoionization–reflectron time-of-flight mass spectrometry together with mass shifts of their isotopically substituted counterparts. The identification of the simplest geminal diol 1’ may have far-reaching consequences for the atmospheric chemistry. Thermodynamically and kinetically stable geminal diols may “lock up” aldehydes and ketones—formed as byproducts of the Criegee-intermediate formation reaction—as geminal diols and hence would remove carbonyl compounds from the atmospheric ozonolysis reaction sequence (1, 13, 14). The Criegee-intermediate formation reaction is a process in which ozone reacts with alkenes forming a carbonyl oxide with two charge centers (Criegee intermediate) (14). Therefore, the existence of geminal diols and Criegee intermediates couples the chemistries of geminal diols, carbonyl compounds, and Criegee intermediates, thus helping to provide a better understanding of the atmospheric chemistry upon which all terrestrial life depends.     

Predictors and Outcomes of Frequent Emergency Department Users

OBJECTIVE: To identify predictors and outcomes associated with frequent emergency department (ED) users. METHODS: Cross-sectional intake surveys, medical chart reviews, and telephone follow-up interviews of patients presenting with selected chief complaints were performed at five urban EDs during a one-month study period in 1995. Frequent use was defined by four or more self-reported, prior ED visits. Multivariate logistic regression identified predictors of frequent ED visitors from five domains (demographics, health status, health access, health care preference, and severity of acute illness). Associations between high use and selected outcomes were assessed with logistic regression models. RESULTS: All study components were completed by 2,333 of 3,455 eligible patients (67.5%). Demographics predicting frequent use included being a single parent, single or divorced marital status, high school education or less, and income of less than $10,000 (1995). Health status predictors included hospitalization in the preceding three months, high ratings of psychological distress, and asthma. Health access predictors included identifying an ED or a hospital clinic as the primary care site, having a primary care physician (PCP), and visiting a PCP in the past month. Choosing the ED for free care was the only health preference predictive of heavy use. Illness severity measures were higher in frequent visitors, although these were not independently predictive in the multivariate model. Outcomes correlated with heavy use include increased hospital admissions, higher rates of ED return visits, and lower patient satisfaction, but not willingness to return to the ED or follow-up with a doctor. CONCLUSIONS: Frequent ED visits are associated with socioeconomic distress, chronic illness, and high use of other health resources. Efforts to reduce ED visits require addressing the unique needs of these patients in the emergency and primary care settings.     

Effect of an educational program on medical students’ conversations with patients about advance directives

Advance directives, such as the durable power of attorney for health care (DPAHC), help patients and physicians make end-of-life health care decisions. Medical education should prepare student physicians to be knowledgeable about and comfortable with discussing advance directives. The authors developed an educational module for the third-year medical school curriculum and conducted a randomized trial to evaluate in students its effect on various outcome measures regarding the DPAHC. Over a six-week period, students who received written material about the DPAHC and a two-hour seminar significantly increased knowledge about and reported increased skill, comfort, and experience with the DPAHC.     

Intra-articular Chlamydial Antigen and Inflammatory Arthritis

Joint material from 133 patients with well-characterized inflammatoryarthritis, including individuals likely to have suffered reactivearthiritis, was studied. The majority of patients were alsoexamined for the presence of genital tract infection with Chlamydiatrachomatis. Fluorescein-conjugated monoclonal antibodies demonstratedthe presence of C. trachomatis antigen in synovial fluid celldeposits or synovial sections from inflamed knee joints of sevenpatients with reactive arthritis. The significance of thesefindings is discussed, as is the low rate of detection of chlamydialantigen in either the genital tract or the joint from patientsin this study. We emphasize the need for further work aimedat identifying the relevant immunogenic chlamydial antigensresponsible for the initiation of reactive arthritis.