Predicting spontaneous racemate resolution using recent developments in crystal structure prediction

NoA hybrid molecular mechanics and quantum mechanics solid state DFT method is used to re-rank the stability of racemic and enantiopure crystal structures of four molecules; 4-hydroxymethyl-2-oxazolidinone, 5-hydroxymethyl-2-oxazolidinone, 2-(4-hydroxyphenyl)-2,5,5-trimethylpyrrolidine-1-oxy and 2-(3-hydroxyphenyl)-2,5,5-trimethylpyrrolidine-1-oxy. Previous work using a force field based method to predict these crystal structures indicated that the lattice energy may be a suitable criterion for predicting whether a chiral molecule will resolve spontaneously on crystallisation. However, in some cases, the method had predicted an unrealistically high lattice energy for the structure corresponding to the experimentally observed one. The Hybrid DFT method successfully predicts those molecules which resolve spontaneously and furthermore predicts satisfactory lattice energies for all experimentally observed structures. Based on a comparison of the predicted lattice energies from the two methods it is concluded that the force fields used were not sufficiently accurate to predict spontaneous resolution with any confidence. However, the Hybrid DFT method is shown to be sufficiently accurate for making such predictions

Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Acquisition Is Associated With Individual Exposure but Not Community-Level Transmission

Abstract Background Transmission rates after exposure to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–positive individual within households and healthcare settings varies significantly between studies. Variability in the extent of exposure and community SARS-CoV-2 incidence may contribute to differences in observed rates. Methods We examined risk factors for SARS-CoV-2 infection in a randomized controlled trial of hydroxychloroquine as postexposure prophylaxis. Study procedures included standardized questionnaires at enrollment and daily self-collection of midturbinate swabs for SARS-CoV-2 polymerase chain reaction testing. County-level incidence was modeled using federally sourced data. Relative risks and 95% confidence intervals were calculated using modified Poisson regression. Results Eighty-six of 567 (15.2%) household/social contacts and 12 of 122 (9.8%) healthcare worker contacts acquired SARS-CoV-2 infection. Exposure to 2 suspected index cases (vs 1) significantly increased risk for both household/social contacts (relative risk [RR], 1.86) and healthcare workers (RR, 8.18). Increased contact time also increased risk for healthcare workers (3–12 hours: RR, 7.82, &amp;gt;12 hours: RR, 11.81, vs ≤2 hours), but not for household/social contacts. County incidence did not impact risk. Conclusions In our study, increased exposure to SARS-CoV-2 within household or healthcare settings led to higher risk of infection, but elevated community incidence did not. This reinforces the importance of interventions to decrease transmission in close contact settings. </jats:sec