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.     

Nomogram of peripapillary retinal nerve fiber layer thickness in myopic eyes of north Indian population

Purpose:To evaluate peripapillary-RNFL thickness in myopia by Cirrus OCT among north Indian population by spherical equivalent (SE), age, gender, and axial length (AL).Methods:This was a cross-sectional study held during 2019–2020. Patients aged 18–60 years underwent ophthalmic examination including retinoscopy, AL, and OCT RNFL thickness. Persons with previous ocular surgery or ocular ailment other than refractive error were excluded. The peripapillary-RNFL thickness was noted and compared by demographic determinants.Results:We examined 300 eyes of 300 persons (mean age: 30.75 ± 8.57 years; 144 males/156 females). Among them, 224 were myopes and 76 were emmetropes (EM). The mean SE was − 3.3 ± 0.4D (range: −11.0D to + 0.37D). The mean AL was 24.61 ± 1.92 mm (22.1–29.5). Overall temporal, nasal, superior, inferior, and mean peripapillary-RNFL thickness was 66.31 ± 7.58, 78.57 ± 16.00, 120.63 ± 11.69, 116.60 ± 15.80, and 95.50 ± 10.84 mm, respectively. Temporal, nasal, superior, inferior, and mean peripapillary-RNFL thickness was 73.97 ± 8.36, 94.84 ± 7.63, 127.96 ± 8.96, 136.89 ± 6.53, and 108.34 ± 6.28 mm, respectively, in EM eyes as compared to 63.71 ± 6.18, 73.05 ± 14.24, 118.21 ± 11.53, 109.71 ± 11.50, and 91.14 ± 8.31 mm, respectively, in myopic eyes (P < 0.001). Association of peripapillary-RNFL thickness with myopia and its different grades was P < 0.001. Association of mean peripapillary-RNFL thickness with age was P > 0.005 and gender was P = 0.168. Correlation between SE and RNFL thickness was positive and significant. Correlation between AL and RNFL thickness was negative but statistically significant. Association of AL with SE was P < 0.001.Conclusion:We provide normative peripapillary-RNFL thickness in the north Indian population in order to help in screening for myopia with comorbidity such as glaucoma based on RNFL thickness.     

Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice

As existing vaccines fail to completely prevent COVID-19 infections or community transmission, there is an unmet need for vaccines that can better combat SARS-CoV-2 variants of concern (VOC). We previously developed highly thermo-tolerant monomeric and trimeric receptor-binding domain derivatives that can withstand 100 °C for 90 min and 37 °C for four weeks and help eliminate cold-chain requirements. We show that mice immunised with these vaccine formulations elicit high titres of antibodies that neutralise SARS-CoV-2 variants VIC31 (with Spike: D614G mutation), Delta and Omicron (BA.1.1) VOC. Compared to VIC31, there was an average 14.4-fold reduction in neutralisation against BA.1.1 for the three monomeric antigen-adjuvant combinations and a 16.5-fold reduction for the three trimeric antigen-adjuvant combinations; the corresponding values against Delta were 2.5 and 3.0. Our findings suggest that monomeric formulations are suitable for upcoming Phase I human clinical trials and that there is potential for increasing the efficacy with vaccine matching to improve the responses against emerging variants. These findings are consistent with in silico modelling and AlphaFold predictions, which show that, while oligomeric presentation can be generally beneficial, it can make important epitopes inaccessible and also carries the risk of eliciting unwanted antibodies against the oligomerisation domain.     

An Indian Boy with Griscelli Syndrome Type 2: Case Report and Review of Literature

Griscelli syndrome 2 is a rare autosomal recessive disorder of pigmentary dilution of hair, skin, splenohepatomegaly, pancytopenia, immune and neurologic dysfunction. Clinical course is characterized by recurrent infection triggered by uncontrolled T-lymphocyte and macrophage activation, called hemophagocytic syndrome. Since the primary presentation is with depigmented hair, we attempt to highlight diagnostic difficulties in such cases in developing countries like ours where pigmentary changes in hair and skin are commonly attributed to severe malnutrition. We also evaluated phenotype of all 10 cases of genotype (c.C550T; p.R184X), collected from published literature worldwide and emphasize the potential role of above mutation as hotspot in Southeast Asian region.     

An isoelectric focusing overlay study of the humoral immune response in Theiler's virus demyelinating disease

Oligoclonal immunoglobulin G (IgG) bands are a frequent feature of inflammatory diseases of the central nervous system (CNS). In multiple sclerosis (MS), cerebrospinal fluid (CSF) oligoclonal IgG bands are a potential clue to the pathogenesis of the disease; however, their particular antigenic target is unknown. We sought to characterize the IgG response in an experimental CNS persistent demyelinating infection by isoelectric focusing (IEF) studies of serum and CSF from mice infected with Theiler's murine encephalomyelitis virus (TMEV). Following IEF, we used a new technique in order to identify TMEV-specific antibodies; focused immunoglobulins were blotted onto nitrocellulose paper which was then overlaid with radiolabeled virus. Autoradiograms showed that most of the TMEV antibody was locally synthesized within the CNS since CSF, but not serum, TMEV antibody had an anodal distribution. CSF IEF TMEV antibody spectrotypes were very similar, presumably because the CSFs were collected from the same inbred mouse strain. CSF TMEV antibody displayed less restricted heterogeneity than the very restricted cathodal CSF oligoclonal IgG bands seen in MS. The new IEF immunoblotting antigen overlay technique will be a powerful detection system to probe for the antigenic target against which MS CSF IgG may be directed.     

Streptozotocin-induced diabetes in the spontaneously hypertensive rat.

Spontaneously hypertensive rats (SHR) were more sensitive to the diabetogenic effects of streptozotocin than normotensive Wistar-Kyoto (WKY) rats. Thus, 10 days after intravenous administration of 25 mg/kg streptozotocin in SHR, mean pancreatic insulin content was decreased by 42% (p less than 0.05), and mean plasma glucose concentration was increased from 85 to 215 mg/dl (p less than 0.001), whereas between 37.5 and 50 mg/kg of streptozotocin was required to produce similar effects in normotensive WKY rats. Also, there was a progressive decrease in blood pressure in SHR injected with 25, 35.7, or 50 mg/kg of streptozotocin, whereas blood pressure was progressively increased after streptozotocin in normotensive WKY rats. The opposite effects of streptozotocin-induced diabetes on blood pressure in SHR and WKY rats could be observed at similar degrees of hyperglycemia and are presently unexplained.     

The Impact of “COVID-19” and “Webinar Pandemic” on Plastic Surgery Practice in Teaching Institutes and Resident Training—A Multicentric Perspective

Introduction  The study was carried out to quantify the changes induced by the pandemic in plastic surgery practice and training and to study the impact of the webinars on plastic surgery education from a residents’ perspective. Methods  In this multicentric study, the number and type of surgeries, cause of injuries, and their regional variation during the coronavirus disease 2019 (COVID-19) period (February–September 2020) were compared with pre–COVID-19 time. An online survey on the impact of webinars was conducted for plastic surgery trainees across the country. Results  There was a significant reduction in total number of surgeries ( p = 0.003). The procedures for hand ( p = 0.156), faciomaxillary injuries ( p = 0.25), and replantations ( p = 0.46) were comparable; there was a significant reduction in combined orthopedic-plastic-surgical procedures ( p = 0.009) during the pandemic. There was a significant reduction in road accidents ( p = 0.007) and suicidal injuries ( p = 0.002) and increase in assault ( p = 0.03) and domestic accidents ( p = 0.01) during the COVID-19 period. A usefulness score of >8 was given for the webinars by 68.7% residents. There was no significant difference in perception of utility when correlated with the academic program at their institutes ( p = 0.109); 92% opined webinars should continue in post-COVID times. Conclusion  There was a drastic reduction in number of elective and emergency procedures during the COVID-19 time, negatively affecting resident training program. Majority of residents felt that webinars could prove a useful adjunct to training in formal training program in post-COVID-19 scenario.